It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the 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.

Part 1. Overview Information
Part 2. Full Text of the 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

A distinction can be drawn between knowledge deficits and novel research opportunities. While novel research presents an opportunity to advance scientific understanding, knowledge deficits often lie within heterogeneously studied areas that are not considered novel and often occur due to variation in underlying biology across development or inter-individual differences. It is the objective the Maternal and Pediatric Precision in Therapeutics (MPRINT) Hub to address both knowledge deficits and novel research through knowledge aggregation and dissemination through the MPRINT Knowledge and Research Coordination Center (KRCC), and via novel research around knowledge deficits conducted by the MPRINT Centers of Excellence in Therapeutics (CETs). These components of the MPRINT Hub will function collaboratively to build a cohesive and integrated national resource to facilitate and catalyze research and drug development in maternal and pediatric therapeutics. For the MPRINT Hub, an additional aspect is assuring that research, both novel and for knowledge deficits, is focused on the goal of improving regulatory science and the drug development process.

While there has been a dramatic increase in biomedical knowledge and a growing number of potential disease targets, there remain significant unmet needs in the treatment of children across the spectrum of pediatric development and of women attempting to conceive, during pregnancy, the post-partum period, and throughout lactation. There is a clear need to improve upon past and current approaches to the study of pharmacology and therapeutics in maternal, post-partum, and pediatric populations. Additionally, individuals in these populations with mental or physical disabilities are often excluded from therapeutics research, leading to a paucity of data for their treatment. The goal of precision medicine is to give the right drug to the right person for the right condition at the right time. To enable this approach, there must be an increase in the understanding of the underlying biological heterogeneity relevant to therapeutics across the continuum of pediatric development and during and around pregnancy.

For the purpose of this FOA maternal and pediatric therapeutics is defined to encompass:

• Therapeutic treatment of obstetric and breastfeeding conditions;
• Physiological changes that occur in a woman’s body during pregnancy, the post-partum period, and during lactation that impact the distribution or effects of administered therapeutics;
• Passage of drug from mother to fetus during pregnancy and to child during breastfeeding, including the effects of those drugs on the fetus or child;
• Therapeutic treatment of pediatric disease, particularly where there are unique pediatric conditions or pharmacodynamic differences from adult disease;
• Physiological changes that occur across the entire spectrum of pediatric development from birth through adolescence that impact the distribution or effects of administered therapeutics.

There are significant barriers to the extension and application of transformative biomedical advances to enable and provide precision medicine to maternal and pediatric populations, including those with disabilities. One barrier is the lack of a centralized resource for high quality, curated knowledge of maternal and pediatric therapeutics that includes the inter-individual variability in underlying biological processes that influence drug disposition and action. Another barrier is the development and integration of research approaches and tools to both facilitate the closing of knowledge deficits, enhance regulatory science, and to facilitate clinical trials in maternal and pediatric populations. Enhancing the availability of knowledge, regulatory science, and drug development tools will facilitate safer, more inclusive, and more cost-effective trials to increase knowledge around use of existing drugs and enable novel drug development. The MPRINT Hub will be a national resource to aggregate, present and expand the available knowledge, tools, and expertise in maternal and pediatric therapeutics to the broader research and drug discovery and development communities.

This FOA invites applications for the administrative structure and technical and scientific infrastructure needed to support MPRINT Hub activities, including knowledge and tools emerging from complementary Centers of Excellence in Therapeutics (RFA-HD-21-026). The MPRINT Hub will create a broadly accessible, integrated platform in maternal and pediatric therapeutics research to facilitate research, regulatory science, drug development, and synergy across the broader scientific community. Within the MPRINT Hub, the KRCC will serve as a centralized knowledge and tool repository and resource, provide overall administrative coordination for the MPRINT Hub, and oversee an Opportunity Pool of funds. To maximize scientific exchange and accelerate research in that field, all information, data, protocols, resources, and methods developed by MPRINT KRCC investigators will be shared within the MPRINT Hub and with the research community at large.

The MPRINT KRCC will use existing data on pediatric ontogeny, physiological changes during pregnancy and lactation, and pharmacometric models as a foundation upon which to add and integrate additional omics data types, phenotype data, and functional genetics studies to enable precision therapeutics for maternal and pediatric populations, including people with disabilities. The MPRINT KRCC will identify key deficits in this accumulated knowledge, which will re-direct the ongoing activities of the KRCC and CETs via the MPRINT Hub’s Steering Committee as well as inform priorities for the NICHD. The MPRINT KRCC itself will not generate new experimental data, but rather will serve as a curated repository, analytical platform, and portal for publicly available data, analytical tools, and indexing of key physical repositories.

The results and resources of the MPRINT KRCC will accelerate the pace of maternal and pediatric therapeutics research to ultimately improve the care of patients by providing the framework, data, evidence, and tools to:

• Adapt existing, and if necessary develop, common data elements for maternal and pediatric therapeutics research;
• Harmonize across electronic health records and electronic data capture systems for identification and tracking of research tools, data, and specimens;
• Model and simulate dosing, toxicity, and efficacy in a continuum of pediatric populations and pregnant and lactating women, including those with disabilities;
• Develop and provide publicly available resources and expertise in physiologically-based pharmacokinetic/pharmacodynamic models and their use in model informed drug development;
• Provide the expertise and infrastructure needed for data management, including standardized acquisition, harmonization, annotation, quality control, timely dissemination, and public accessibility;
• Additionally, the MPRINT KRCC will:
• Serve as the primary portal for the national scientific community to the MPRINT KRCC, the MPRINT CETs, and potential future MPRINT Hub components;
• Provide for overall logistical coordination of all activities among all MPRINT Hub components;
• Oversee an Opportunity Pool to solicit and fund additional projects based on emerging needs and to leverage newer technologies.

By providing access to these resources to the research, regulatory science, and drug development communities, the MPRINT KRCC will accomplish its goal of conducting and facilitating research leading to precision medicine approaches in maternal and pediatric therapeutics. To maximize scientific exchange and accelerate research in that field, it is expected that all information, data, protocols, resources, and methods developed by MPRINT KRCC investigators will be shared in a timely way with other investigators in the MPRINT Hub and with the research community at large.

Activities of the MPRINT KRCC will be undertaken with input from a Steering Committee composed of MPRINT Hub awardees in addition to feedback from the MPRINT Hub’s External Program Consultants (EPCs) and the NICHD.

Knowledge Base and Portal

The Knowledge Base and Portal of the MPRINT KRCC will serve as the primary database, integrator, and analytical platform for publicly available data and knowledge around precision medicine for children and pregnant and lactating women, including data produced by other components of the MPRINT Hub such as the CETs (RFA-HD-21-026). It will possess a publicly accessible presentation layer (front-end) for display of aggregated data and knowledge usable by a variety of user types. It may serve this function for certain publicly available data types generated by other, highly relevant NICHD research endeavors. The MPRINT KRCC Knowledge Base and Portal should possess the following characteristics:

• Provide a common, curated catalog of pharmacokinetic and pharmacodynamic data for children and pregnant and lactating women, including those with disabilities;
• Incorporate data from studies of pediatric ontogeny and the physiological changes that occur with and around pregnancy and lactation that influence drug metabolism, distribution, and drug response;
• Address priority knowledge deficits including pharmacogenomics, pharmacometric modeling, ontogeny of drug metabolizing enzymes and transporters, and biomarkers;
• For pediatrics, address priority knowledge deficits that relate to the priorities of the Best Pharmaceuticals for Children Act (https://www.nichd.nih.gov/sites/default/files/inline-files/2020PriorityListFeb20.pdf);
• Provide download access to as many underlying data sets as possible to registered users that agree to an end user agreement;
• Develop a publicly accessible portal of its aggregate knowledge which should have, at least, the following characteristics:
• Usability by a variety of user types (e.g., clinicians, researchers, pharmacologists);
• Allow users to perform analyses and visualizations of its underlying data and knowledge base;
• Identify sections of knowledge that would ideally be accessible through portable devices (e.g., tablets, phones, etc) and develop Apps for their access;
• Interface with other knowledge portals to provide access to additional data types not directly supported by the MPRINT Hub (e.g., PharmGKB, Pharos, AMP T2D KP).

Pharmacometrics and Clinical Trial Design Core

The Pharmacometrics and Clinical Trial Design Core will serve as a national resource to provide state of the art pharmacometric models and expertise for dose selection in maternal and pediatric clinical trials. This will enable more accurate and precise dosing so that trials initiated in these populations will begin with the highest likelihood of accurate, safe, and effective dosing using the smallest number of participants. The Pharmacometrics and Clinical Trial Design Core should possess the following characteristics:

• Provide a locus of highly experienced pharmacometricians to assist with development and analysis of therapeutic studies;
• Develop physiologically-based pharmacokinetic-pharmacodynamic (PBPK-PD) models adaptable to change with development and growth;
• Establish a process for evaluating data quality and adjudicating which data to include versus not include in PBPK-PD models;
• Begin to incorporate pharmacogenomic variation, disease processes, biomarkers of disease processes and therapeutic response, and factors related to disability in to pharmacometric models;
• Serve as a centralized access point to state of the art computational and systems models for maternal and age-specific pediatric model informed drug discovery.

Outreach, Dissemination, and Training Core

The Outreach, Dissemination, and Training Core of the MPRINT KRCC will conduct and support a variety of activities relating to interactions between the MPRINT Hub and the broader scientific community. These activities will include, but are not limited to:

• Promote the capabilities of the MPRINT Hub, assessing the needs of the broader scientific community, and monitoring community access of MPRINT Hub components in order to guide ongoing and future MPRINT Hub activities;
• Ensure the rapid and timely sharing of MPRINT Hub generated data and resources within the Hub and with the broader scientific community;
• Conduct an annual scientific meeting on maternal and pediatric therapeutics;
• Provide training opportunities for investigators outside of the MPRINT KRCC in areas of its expertise (e.g., administration, collated data analyses, data dissemination, pharmacometric modeling, etc.);
• Host an annual virtual lecture series on maternal and pediatric therapeutics that incorporates basic and foundational learning as well as emerging, cutting edge advances in the field.

Logistics Core

The Logistics Core will provide for overall logistic and administrative coordination of the MPRINT Hub’s efforts, including those of the MPRINT KRCC, the MPRINT CETs (RFA-HD-21-026), and any future components as well as oversee use of the Opportunity Pool funds. These activities will include, but are not limited to:

• Facilitate coordination of MPRINT KRCC activities and findings with other related database efforts;
• Facilitate scientific interactions across the entire MPRINT Hub using regular teleconferences of committees, and scientific or administrative working groups and organizing face-to-face meetings of MPRINT Hub awardees;
• Provide administrative support and as needed resources for other Cores in the MPRINT KRCC;
• Manage the solicitation, evaluation, and award of subcontracts on a yearly basis from an Opportunity Pool that will support activities such as, but not limited to:
• Expansion of a Core within the MPRINT Hub to handle greater than expected demand from the broader scientific community;
• Establish a new Core function within the MPRINT Hub to address emergent needs in maternal and pediatric therapeutics;
• Generation of new computational or experimental tools that may enhance precision dosing in maternal and pediatric populations.

Optional Core

The KRCC may propose at most one Optional Core. The Optional Core would be intended to support the other Cores within the proposed KRCC and provide support services to other components of the MPRINT Hub, if applicable. An Optional Core may be made available as a national resource. An Optional Core is not required to be fully operational at the start of the KRCC and may include efforts to develop and implement their functions during the first two years of the KRCC award. However, preliminary data supporting feasibility of achieving functional Optional Core of the third year of awards must be shown.

Activities of Optional Cores may include, but are not limited to:

• Utilize pre-clinical animal studies to generate data to inform pharmacometric models, such as through determining partition coefficients for commonly used drugs;
• Establish predictive cell-based, ex vivo, animal, or biomimetic models of disease or drug response that account for heterogeneity of disease and individual variation in genetics and developmental trajectory.

A Steering Committee (SC) will be formed to provide overall direction and guidance for the MPRINT KRCC and CET (RFA-HD-21-026) awardees collectively the MPRINT Hub. The Chair(s) of the SC will be selected by the NICHD from the PDs/PIs of the MPRINT Hub awardees. The MPRINT SC will establish procedures for the function of the Hub, including monthly SC teleconferences and, as necessary, convene working groups of the SC for specific purposes. Such working groups should be composed of at least one PD/PI from an MPRINT Hub award, at least one senior/key personnel from each MPRINT Hub awardee, and ex officio NIH members as well as other necessary MPRINT Hub members, external scientists, and/or External Program Consultants (EPCs), as needed. At least once yearly, the Steering Committee and other key personnel are expected to convene an in-person meeting (or virtual equivalent) to review scientific progress, highlight key Hub activities, and communicate with NICHD staff. The MPRINT Hub will establish strong working relationships with other related efforts, including collaborative projects, and will share scientific approaches and data prior to publication. NIH staff from other NIH-funded networks may participate as ex officio members in the MPRINT Hub SC and/or its working groups.

External Program Consultants will be selected by the NICHD to review the functioning and progress of the Hub and ensure the Hub is operating optimally and efficiently. EPCs will be appointed by the NICHD on a yearly basis and may include, but is not limited to, persons with expertise in data sciences, clinical pharmacology, pediatric subspecialties, maternal health, clinical trial design and analysis, developmental biology, and regulatory sciences. EPCs may be members of other Federal Agencies such as the Food and Drug Administration, Centers for Medicare and Medicaid Services, or others as deemed necessary by the NICHD. The NICHD, after consulting with the EPCs, may request modification to research projects or cores across the MPRINT Hub, including re-prioritization of effort among research projects and/or cores across the MPRINT Hub.

Evaluation of the MPRINT Hub by EPCs will include, but is not limited to:

• Progress of member Center programs;
• Proposed new research efforts within scope of the approved program;
• Collaborative needs either within or outside the MPRINT Hub;
• Evaluation and adjustment of the process used to solicit, evaluate, and select Opportunity Pool projects;
• Need to redirect efforts of member Centers based on emergent science, lack of productivity, or underutilization of resources by the broader scientific community.

Applications that are not responsive to this funding announcement:

Projects listed below are not within the scope of this funding announcement.  Applications proposing out of scope projects are not responsive to this FOA and will not be reviewed.

• Applications that propose to conduct clinical trials;
• Applications that propose non-computational research outside of the Optional Core;
• Projects not focused on maternal and pediatric pharmacology and therapeutics research as defined above;
• KRCC proposals that are not focused on open access of its resources to investigators across the nation.

Pre-application Informational Webinar

An informational webinar for this announcement and its companion announcement will be held on Thursday, October 8th, 2020 at 1 PM - 3 PM, Eastern time. Potential applicants are encouraged to attend. Frequently Asked Questions from the webinar will be made publicly available. The FAQs and additional information on the webinar can be obtained at - https://www.nichd.nih.gov/about/org/der/branches/opptb/mprint. The webinar is optional and not required for application submission.

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

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

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)

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)
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not 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.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• 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.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 DUNS number and 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 underrepresented racial and ethnic groups as well as individuals with disabilities 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.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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.  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 NOT-OD-11-101).

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

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:

Lesly-Anne Samedy-Bates, M.S., Pharm.D., Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-827-3241
Email: lesly-anne.samedy-bates@nih.gov

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Knowledge Portal: Use for Knowledge Base and Portal	12
Pharmacometrics Core: Use for Pharmacometrics and Clinical Trial Design Core	12
Outreach Core: Use for Outreach, Dissemination, and Training Core	6
Logistics Core	6
Optional Core	6

Additional page limits 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 a multi-component application.

The application should consist of the following components:

• Overall: required; maximum of one
• Knowledge Base and Portal: required; maximum of one
• Pharmacometrics and Clinical Trial Design Core: required; maximum of one
• Outreach, Dissemination, and Training Core: required; maximum of one
• Logistics Core: required; maximum of one
• Optional Core: optional; maximum of one

When preparing your application, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: Describe the aims of the overall MPRINT KRCC and outline how the different Cores will contribute to these aims. State how the Cores will promote the NICHD’s 2020-2024 Strategic Plan (https://www.nichd.nih.gov/about/org/strategicplan), in particular (1) research theme five’s focus on advancing safe and effective therapeutics for pregnant and lactating women and children, including those with disabilities; and (2) the NICHD’s scientific stewardship of promoting an inclusive scientific workforce that fosters research training and facilitating data sharing.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation, and Approach.

Significance: Focusing on the MPRINT KRCC as a whole address:

• The importance of the problems and critical barriers to advancing drug development in maternal and pediatric therapeutics that the proposed MPRINT KRCC will focus on;
• How the resources of the proposed KRCC will improve scientific knowledge, technical capability, and enable maternal and pediatric therapeutics research and drug development;
• How the concepts, methods, technologies, and/or approaches that drive maternal and pediatric therapeutics will be changed if the proposed aims are achieved.

Innovation: Considering the MPRINT KRCC as a whole, describe how the proposed resources will:

• Serve to shift current maternal and pediatric clinical research and/or drug development paradigms through use of novel tools, approaches, methodologies, and/or modeling;
• Accelerate translational research across the spectrum of pediatric disease and maternal conditions, with a strong focus on understanding disease heterogeneity;
• Provide an environment and resources to enhance cutting-edge clinical research and drug development by bringing together investigators from various fields to identify and address the knowledge deficits in delivering precision dosing to maternal and pediatric populations;
• If applicable, demonstrate scientifically productive interactions across related NICHD and NIH, FDA, VA, or other federally funded resources, clinical networks, or projects.

Approach: Applicants should address, at a minimum, the following aspects:

• Describe how all of the Cores of the MPRINT KRCC complement each other and provide a plan for how the investigators will work together including preliminary evidence of interactions;
• Describe the mechanisms that will ensure the coherence of the KRCC and maintain a multidisciplinary focus and leverage team science;
• Describe preliminary organizational work, experience with maternal and pediatric pharmacology research, potential for developing or contributing to new and exciting research, and specific plans for implementation of the new MPRINT KRCC;
• Discuss the interrelation of the MPRINT KRCC to other activities in the applicants institution(s) (e.g., other relevant research projects) and the extent of institutional, departmental, and interdepartmental cooperation and support (charts and tables may be included);
• Describe how the MPRINT KRCC will ensure that the necessary infrastructure is in place to facilitate broad data sharing, consistent with the goals of the program;
• Clearly state the overall MPRINT KRCC deliverables, timelines, and milestones and how they align to the overall goals of the MPRINT Hub;
• Describe how the MPRINT KRCC will reprioritize and adjust activities, deliverables, timelines, and milestones on an annual basis (in the RPPR) based on feedback from the MPRINT Hub SC, External Program Consultants, and NICHD staff.

The NICHD may negotiate changes to the MPRINT KRCC deliverables, timelines, and milestones as well as the process for their reprioritization prior to award.

Letters of Support: A letter from each participating institution stating its commitment to support the proposed KRCC and its integration into ongoing activities at the applicant's institution should be provided.

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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan for the full KRCC in the Overall component of the application.

Applicants should indicate their willingness to abide by all data deposition, quality control metrics, standardization, metadata requirements, data and software release, and public copyright license policies developed by the MPRINT Hub SC and approved by NICHD staff. A primary goal of the MPRINT Hub is to facilitate discoveries of the broad scientific community for the improvement of public health. Restrictive licensing and sharing practices for Hub-generated data, tools, and resources could substantially diminish their value and public benefit. Accordingly, awardees should manage data, resources, protocols, tools, and software in a way that achieves this goal. The NICHD expects that the awardees, through the MPRINT Hub SC, will develop such policies, methods, and standards in concert with the NICHD. These policies, methods, and standards will remain consistent with NIH-wide and NICHD policies on data and resource sharing.

Specific Plan for Data Sharing: Consistent with achieving the goals of this program, the NICHD expects that information such as collected data, technical protocols, and any other metadata collected under this FOA is to be deposited as appropriate into existing, publicly available data repositories that are easily accessible, and in machine readable format. For human data, the NICHD encourages the use of the Data and Specimen Hub (DASH), a centralized resource for researchers to store and access de-identified data from studies funded by NICHD. Where appropriate, applicants should identify such repositories and plans for deposition. For datatypes that lack suitable public repositories, applicants should indicate their willingness to identify an appropriate alternative solution that is consistent with achieving the goals of the program. Data should also be made available as appropriate via the MPRINT Hub Knowledge Base and Portal that will serve as the central access point for information regarding data, critical tools, and reagents being developed by the MPRINT Hub. If applicable, applicants must abide by the NIH Genomic Data Sharing Policy (https://osp.od.nih.gov/scientific-sharing/genomic-data-sharing/) and should indicate their agreement to it in the data sharing plan.

Specific Plan for Protocol, Tool, and Reagent Sharing: In accomplishing the goals of the MPRINT Hub, it is likely that investigators will develop protocols, tools, and reagents that would be of broad use in the research community. The NICHD intends that protocols, tools, and reagents generated by the MPRINT Hub be broadly available and distributed at minimal cost, and without undue intellectual property constraints, so that they can be as widely used as possible, thus enabling downstream investigations in maternal and pediatric therapeutics. For all applications where applicable, the applicant should discuss plans for sharing and distribution of non-data resources that will be generated by the proposed project, including models, protocols, biomaterials, and reagents.

Specific Plan for Sharing Software: A software dissemination plan is expected in applications that are developing software. There is no prescribed single license for software produced in this project; however, reviewers will be asked to evaluate the software sharing and dissemination plan based on its likely impact. Applicants are asked to propose a plan to manage and disseminate the improvements or customizations of their tools and resources by others. This proposal may include a plan to incorporate the enhancements into the official core software, may involve the creation of an infrastructure for plug-ins, or may describe some other solution. A dissemination plan guided by the following principles is thought to promote the largest impact:

• The software should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of training, research institutions, and government laboratories.
• The terms should permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.
• The software should be transferable such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so.
• The terms of software availability should include the ability of researchers outside of the MPRINT Hub and its collaborating projects to modify the source code and to share modifications with other colleagues. An applicant should take responsibility for creating the original and subsequent official versions of a piece of software.

Applicants should also be familiar with the NIH statements regarding intellectual property of resources developed with Federal funds (NIH Research Tools Policy (http://grants.nih.gov/grants/intell-property_64FR72090.pdf) and other related NIH sharing policies at http://sharing.nih.gov).

Prior to funding, NICHD Program Staff may negotiate modifications to the Sharing Plan with the applicant.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

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.

When preparing your application, use Component Type Knowledge Portal.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• This Project Leader's biosketch should reflect awareness of, and experience with, database management practices, statistics, bioinformatics, and user interface design and assessment. The Project Leader may be primarily a data manager or user interface designer. The Project Leader should have the time and the authority to work administratively with other cores. The Project Leader should have a publication track record with other key personnel at the Center.
• The core should include: (1) A systems manager for computing and database management who will be the architect of the database structure and responsible for its maintenance; (2) A systems analyst with sufficient background to select and implement database management software, represent data structures, specify and organize data flow, construct detailed error-check programs, develop/implement data checking and cleaning procedures, and provide for data entry and access, as well as information distribution, through electronic means (e.g., the internet or intranet); (3) A user interface designer who is experienced with designing and deploying web infrastructure that can incorporate analytical and visualization tools as well as experience in conducting user experience assessments to assure usability to a broad variety of users.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Clearly state how the Knowledge Base and Portal will:

• Contribute to the goals of the MPRINT Hub and outline interactions of the Core with each of the other components of the MPRINT KRCC;
• Aggregate and curate knowledge around drug metabolism, transport, and action and across the spectrum of pediatric development from premature birth through adolescence, during the natural course of pregnancy, the post-partum period, and during lactation;
• Utilize the aggregated and curated knowledge to assemble a comprehensive mineable knowledgebase and to identify knowledge deficits;
• Describe database, knowledgebase, and web portal services that will be provided within the MPRINT Hub and to the broad scientific community to mind the aggregated and curated knowledge.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation and Approach.

Significance: Explain the role of the Knowledge Base and Portal in the MPRINT KRCC as a whole and as a resource for other ongoing activities within the field of maternal and pediatric therapeutics. Explain how the knowledge aggregated and presented by the core will ultimately lead to advances in clinical trial design, conduct, and efficiency.

Innovation: For the Knowledge Base and Portal, show how the proposed activities seek to shift the status of knowledge in maternal and pediatric therapeutics and drug development paradigms through use of novel concepts, approaches, methodologies, instrumentation, or interventions.

Approach: Applicants should describe how their team proposes to handle, at a minimum, the following required functions:

• Using existing efforts and standards (e.g., FHIR, CD2H) as a starting point, lead efforts to adapt (and when necessary, develop) common data elements for maternal and pediatric therapeutics research and provide for harmonization across electronic health records, electronic data capture systems, and publicly available information sources;
• Bring in, curate, and house publicly available data on pediatric ontogeny and physiologically based changes that occur during pregnancy and lactation that relate to drug metabolism, disposition, and response;
• Use current automated, AI-driven data analytic and bioinformatics technologies to automatically and systematically collect, analyze, and integrate relevant data from across the public domain (e.g., electronic health records, literature, existing databases and registries such as PharmGKB, Pharos, PregSource etc.);
• Develop a platform to integrate data and knowledge around maternal and pediatric drug metabolism, disposition, and response in order to rank quality and reliability of knowledge and identify key deficits for research within the MPRINT CETs and elsewhere;
• Describe how the core will use initial data collection and analyses to assess the status of various therapeutic areas and specific diseases in order to prioritize areas for focus throughout the award period;
• For pediatrics, describe how the focus of priority areas of the Knowledge Base and Portal relate to the priorities of the Best Pharmaceuticals for Children Act (https://www.nichd.nih.gov/sites/default/files/inline-files/2020PriorityListFeb20.pdf;
• Interact with the Pharmacometrics and Clinical Trial Design Core to develop and improve pharmacometric models based on the accumulated data of the Knowledge Base and Portal, including developing metrics for data quality and utility for pharmacometrics modeling;
• Develop a user-friendly web portal that researchers can use to explore, analyze, and visualize knowledge and predictions of drug metabolism, disposition, and response across the continuum of pediatric development and maternal conditions;
• Provide means for end users to both download and directly perform analyses on as much raw data as possible and permissible;
• Begin to support precision medicine through analysis and integration of additional multi omics and physiological data where possible, recognizing it may sometimes be more effective to have separate knowledgebases accessed directly by the front-end web portal;
• When needed, seamlessly access and display key data from publicly available databases and other knowledge portals which are not integrated into the MPRINT KRCC Knowledge Base and Portal (e.g., single-cell atlases, protein-centric databases, pathway and network knowledgebases, pharmacogenomic knowledgebases);
• Develop a strategy to regularly monitor and evaluate usability of the system, including other components and sub-components of the MPRINT Hub, by the various MPRINT Hub stakeholders and implement changes to the MPRINT Hub based on feedback;
• Describe strategies to support FAIR data principles as well as use of community standards for data and metadata, data identifiers, provenance of data, adequate infrastructure and storage;
• Define deliverables, timelines, and milestones for the Knowledge Base and Portal Core and how they align with the overall goals of the MPRINT Hub;
• Articulate how the MPRINT KRCC Knowledge Base and Portal will reprioritize and adjust activities, deliverables, timelines, and milestones on an annual basis (in the RPPR) based on feedback from the MPRINT Hub SC, External Program Consultants, and NICHD staff.

The NICHD may negotiate changes to the MPRINT KRCC Knowledge Base and Portal deliverables, timelines, and milestones as well as the process for their reprioritization prior to award.

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, with the following modification:

The Resource Sharing Plan submitted to the Overall component of the application must include elements to address all proposed activities in this component of the application.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a 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.

When preparing your application, use Component Type Pharmacometrics Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• This Project Leader's biosketch should reflect awareness of, and experience with, database management practices, statistics, pharmacometrics, model-informed drug development, and bioinformatics. The Project Leader may be primarily a pharmacometrician or clinical trial design statistician. The Project Leader should have the time and the authority to work administratively with other cores. The core leaders should have a publication track record with other key personnel at the Center.
• The project should include individuals with expertise in clinical trial design, FDA regulatory considerations, and patient recruitment.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Clearly state how the core will:

• Contribute to the overall goals of the MPRINT KRCC and interact with other components;
• Provide a locus of highly experienced pharmacometricians to construct dynamic developmental models for drug distribution, metabolism, and response;
• Use current pharmacometric and model-informed drug development approaches as a framework to incorporate and deploy knowledge collected and aggregated by the MPRINT KRCC’s Knowledge Base and Portal;
• Serve as a national resource for pharmacometrics, model informed drug development, and clinical trial design and analysis for maternal and pediatric therapeutics.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation and Approach. 

Significance: Explain (1) the role of the Core in the KRCC as a whole and how this resource will accelerate and transform ongoing activities in maternal and pediatric therapeutics research and drug development at the applicant’s institution; and (2) how this Core will enable access to dynamic developments in maternal and pediatric therapeutics (e.g., support trials for label changes for pediatric or maternal applications, incorporate utilization of pharmacogenomic variants, predict levels of drug in breast milk);

Innovation: For the Pharmacometrics and Clinical Trial Design Core, show how the proposed activities seeks to shift the status of available tools and approaches in maternal and pediatric therapeutics and drug development paradigms through use of novel concepts, approaches, methodologies, instrumentation, or interventions.

Approach: Applicants should address, at a minimum, the following aspects:

• Provide preliminary data indicating the applicants ability to use and develop physiologically based- pharmacokinetic models for maternal and/or pediatric therapeutics;
• Demonstrate evidence of the ability to serve as a resource for other investigators in the development and deployment of pharmacometric models and clinical trial design and analysis for maternal and/or pediatric therapeutics;
• Summarize the availability of existing pharmacometric models for maternal and pediatric therapeutics and identify key deficits in knowledge and tools;
• Describe how pharmacometric models will be adapted to account for individuals with disability;
• Provide a plan to begin to fill knowledge deficits and develop tools based on the above summary, and how the Knowledge Base and Portal Core will assist in this activity;
• How this Core will work with the Knowledge Base and Portal Core to adapt, and if necessary develop, standards for data quality and utility as it relates to pharmacometrics modeling;
• Begin to support integration of individual-level genomic and other omics data in to pharmacometric modelling to enable precision dosing;
• Describe how access to Pharmacometrics and Clinical Trial Design Core resources will be promoted, both within the MPRINT Hub and within the larger maternal and pediatric therapeutics community;
• Define deliverables, timeline, and milestones for the Pharmacometrics and Clinical Trial Design Core;
• Articulate how the MPRINT KRCC Pharmacometrics and Clinical Trial Design Core will reprioritize and adjust activities, deliverables, timelines, and milestones on an annual basis on an annual basis (in the RPPR) based on feedback from the MPRINT Hub SC, External Program Consultants, and NICHD staff.

The NICHD may negotiate changes to the MPRINT KRCC Pharmacometrics and Clinical Trial Design Core deliverables, timelines, and milestones as well as the process for their reprioritization prior to award.

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, with the following modification:

The Resource Sharing Plan submitted to the Overall component of the application must include elements to address all proposed activities in this component of the application.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a 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

When preparing your application, use Component Type Outreach Core

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

•       In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
•       In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
•       Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
•       If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Clearly state how the core will:

• Contribute to the goals of the MPRINT KRCC and outline interactions of the core with each of the other components of the MPRINT KRCC;
• Summarize the outreach, dissemination, and training objectives of the MPRINT KRCC and plans to assess those of the MPRINT CET awardees;
• Outline outreach, dissemination, and training plans that relate to advancing the fields of maternal and pediatric therapeutics at a national level.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation and Approach.

Significance: Explain how the Outreach, Dissemination, and Training Core will contribute to changing the state of maternal and pediatric therapeutics at a national level through promotion and engagement with the MPRINT Hub’s resources and through conducting training activities.

Innovation: Describe the innovative practices and approaches the Outreach, Dissemination, and Training Core will bring to the field of maternal and pediatric therapeutics.

Approach: Applicants should describe how they will conduct major activities of the Outreach, Dissemination, and Training Core which include, at a minimum, the following:

• How the Outreach, Dissemination, and Training Core will work with the Knowledge Base and Portal Core to coordinate a cohesive web and branding presence so there is a clear primary landing page for the MPRINT KRCC;
• Describe plans to work with the MPRINT CETs to coordinate a cohesive web and branding presence so there is a clear primary landing page for the MPRINT Hub as a whole;
• Develop a strategy to regularly monitor and evaluate how the MPRINT Hub, including its sub-components, is meeting the needs of the nation s maternal and pediatric therapeutic research community (e.g. analyzing web-use statistics, focus groups, evaluating requests for services);
• Run an annual publicly available lecture series on maternal and pediatric and therapeutics that will present core foundational knowledge and communicate cutting edge research developments, which should include a statement of willingness to work with NICHD staff to incorporate this lecture series in to the NICHD’s Virtual Network for pharmacology trainees;
• Ensure that data, tools, models, protocols, biomaterials, resources, and reagents developed by all individual MPRINT Hub investigators are accessible through the MPRINT Hub web portal in a timely manner;
• Facilitate interactions with other NIH-supported research efforts as well as non-NIH partners, which may include consortia, bio-repositories, databases, non-profit organizations, registries, and for profit entities including pharmaceutical companies;
• Manage and facilitate other outreach activities including managing the social media presence of the MPRINT Hub, organizing sessions at scientific meetings, and facilitating opinion and perspective pieces for publication;
• Define deliverables, timelines, and milestones for the Outreach, Dissemination, and Training Core and how they align with the overall goals of the MPRINT Hub;
• Articulate how the MPRINT KRCC’s Outreach, Dissemination, and Training Core will reprioritize and adjust activities, deliverables, timelines, and milestones on an annual basis on an annual basis (in the RPPR) based on feedback from the MPRINT Hub SC, External Program Consultants, and NICHD staff.

The NICHD may negotiate changes to the MPRINT KRCC Outreach, Dissemination, and Train Core deliverables, timelines, and milestones as well as the process for their reprioritization prior to award.

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, with the following modification:

The Resource Sharing Plan submitted to the Overall component of the application must include elements to address all proposed activities in this component of the application.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a 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

When preparing your application, use Component Type Logistics Core .

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The Project Leader should have demonstrated leadership and administrative skills. Specifically, the Project Leader should be able to organize and administer the resources created by the KRCC in such a way that they may be shared within the MPRINT KRCC as well as with other interested scientists. Demonstrated leadership in training junior investigators is desirable.
• The contact Program Director/Principal Investigator of the proposed MPRINT KRCC should also be the Logistics Core Project Leader; sufficient time should be devoted to the core to ensure that the aims are met and required functions are carried out efficiently. The PD/PI’s biographical sketch should present evidence of scientific expertise relevant to the themes of the MPRINT KRCC and demonstrate the capacity for the leadership of the MPRINT KRCC.
• The administrative requirements of the MPRINT KRCC will necessitate the assistance of an administrator with business management expertise. It is important that such an individual be identified and be directly involved with the fiscal and administrative aspects of the MPRINT KRCC application and grant. The administrator should be able to provide consultation in matters of fiscal administration and be familiar with NIH grant-related compliance policies.
• An Associate Director may be named who will be involved in the administrative and scientific efforts of the Center. If this is a multi-PD/PI application, this should be one of the non-contact PD/PIs.

Budget forms appropriate for the specific component will be included in the application package.

A significant time commitment (3.0 person months) should be made between the Project Leader and an Associate Director, with each person having no less than 1.2 person months.

Domestic and foreign travel of personnel directly related to the core and scientific activities of the MPRINT KRCC is allowable. Budgeting should include travel and lodging for representatives of the MPRINT KRCC to both host and attend:

• Annual meetings of the MPRINT Hub PDs/PIs;
• Annual meetings of administrators, core leaders, training core leaders, data managers, and other key personnel;
• Representatives of the MPRINT Hub to attend ad hoc meetings called by the MPRINT Hub or the NICHD to discuss research findings and plan cooperative projects, to promulgate data sharing, and to discuss standardization of procedures within the MPRINT Hub;
• An annual 2-3 day in person scientific meeting (or virtual equivalent) in the Bethesda, MD area, to include budgeting for meeting room space, audiovisual support, meeting materials, etc. for attendees from all components of the MPRINT Hub;
• At least one ad hoc meeting on special topics for attendees from all components of the MPRINT Hub.

Opportunity Pool projects must be budgeted in the Logistics Core budget. A brief description of the first-year Opportunity Pool project solicitation and award process plans for the first year of MPRINT KRCC funding will be requested as Just-in-Time information through the eRA Commons shortly before the award of successful applications. Future-year Opportunity Pool projects should be submitted with the annual Research Performance Progress Report (RPPR). Facilities & Administrative costs will be provided in accordance with these budgets. Opportunity Pool projects may have a project term between 1 and 3 years. Opportunity Pool projects may be awarded to investigators outside of the home institution. Applicants should budget for a total of $500,000 total costs under the other expenses within the Logistics Core budget as a separate line in the composite budget. Opportunity Pool funds will be restricted from use until approved by the NICHD. This line item should be a Direct Cost amount such that when combined with its associated Indirect Costs the total is $500,000 in Total Costs.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Clearly state:

• How the Logistics Core will contribute to the goals of the MPRINT KRCC;
• Outline interactions of the core with each of the other components of the Center;
• Provide an overview of how the Logistics Core will set the overall direction of the MPRINT KRCC and ensure optimal utilization of MPRINT KRCC resources;
• Explain how the Logistics Core will solicit, review, select, and manage awards from the Opportunity Pool funds;
• Explain how the MPRINT KRCC will coordinate with the MPRINT CETs (RFA-HD-21-026) to provide overall logistic coordination and oversite for the MPRINT Hub.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation and Approach.

Significance: Explain the role of the Logistics Core in the MPRINT KRCC, and the Hub as a whole, in establishing the MPRINT Hub as a central resource for national activities in maternal and pediatric therapeutics research. 

Innovation: For the purposes of the Logistics Core, innovation is defined as the business and management approaches that will promote seamless and efficient operation of the MPRINT KRCC and the MPRINT Hub and does not need to include novelty.

Approach: Describe how the MPRINT KRCC’s Logistics Core structure will support, at a minimum, the following:

• Provide evidence of ability to manage a complex multi-site endeavor such as is being proposed, both in terms of the MPRINT KRCC and oversite of integrated projects such as the MPRINT CETs;
• Oversight of research and grants administrative processes (including preparation of annual RPPR)s;
• Coordination and integration of the other MPRINT KRCC Cores components and activities;
• Coordination and organization of external and internal advisory committee meetings;
• Interaction with other components of the MPRINT Hub and other researchers to develop trans-MPRINT Hub activities;
• Organize at least monthly teleconferences of the MPRINT Hub PIs and NICHD staff and at least one annual 2-3 day in person scientific meeting (or virtual equivalent) of the MPRINT Hub investigators, External Program Consultants, and NICHD staff;
• Provide administrative support to various governing or advisory bodies including the MPRINT Hub SC and various subcommittees to facilitate the strategic planning and decision-making process;
• Support travel and logistics for External Program Consultants that will provide input on the direction of the Hub;
• Initiate, facilitate development of, maintain, and make available MPRINT Hub policies, such as for publication and internal data sharing, and other needed policies as determined by the MPRINT Hub SC;
• Assist NICHD-staff with managing the face-to-face MPRINT Hub kick off meeting and then take the lead organizing and managing meeting logistics for the subsequent annual Hub-wide meeting;
• Applicants should also describe how their team proposes to administer Opportunity Pool funds, addressing, at a minimum, the following aspects:
• How the MPRINT KRCC will work with the MPRINT Hub’s Steering Committee, NICHD staff, and potential other funding partners to identify emergent needs on a yearly basis;
• How the MPRINT KRCC will solicit, review, and select internal and external proposals for funding;
• How subcontracts will be overseen and integrated into the overall MPRINT Hub.
• Provide reports to NICHD staff as needed on activities and progress made by the MPRINT Hub;
• Define deliverables, timelines, and milestones for the Logistics Core and how they align with the goals of the MPRINT Hub;
• Articulate how the MPRINT KRCC’s Logistics Core will reprioritize and adjust activities, deliverables, timelines, and milestones on an annual basis (in the RPPR) based on feedback from the MPRINT Hub SC, External Program Consultants, and NICHD staff.
• Describe how the Logistics Core will assist the entire MPRINT Hub SC, NICHD staff, and External Program Consultants to develop and implement plans to adjust activities across the MPRINT Hub to meet the needs of the maternal and pediatric research communities.

The NICHD may negotiate changes to the MPRINT KRCC Logistics Core deliverables, timelines, and milestones as well as the process for their reprioritization prior to award.

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, with the following modification:

The Resource Sharing Plan submitted to the Overall component of the application must include elements to address all proposed activities in this component of the application.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a 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

When preparing your application, use Component Type Optional Core .

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Clearly state how the core will contribute to the goals of the MPRINT KRCC and outline interactions of the core with each of the other cores of the Center.

Describe exactly how the proposed Optional Core would augment or enhance the capabilities of investigators using Center resources to enhance or create research within the MPRINT KRCC as well as the wider research community.

Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation, and Approach. There should be a detailed discussion of the research that will or could use the resources of the Optional Core. Clearly address the deliverables, timelines, and milestones for the Optional Core, how they align with the overall goals of the MPRINT Hub, and how the Core will reprioritize and adjust activities, deliverables, timelines, and milestones on an annual basis (in the RPPR) based on feedback from the MPRINT Hub SC, External Program Consultants, and NICHD staff.

The NICHD may negotiate changes to the MPRINT KRCC Optional Core deliverables, timelines, and milestones as well as the process for their reprioritization prior to award.

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, with the following modification:

The Resource Sharing Plan submitted to the Overall component of the application must include elements to address all proposed activities in this component of the application.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a 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.

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) using ASSIST or other electronic submission systems. 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.

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.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. 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.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). 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, non-compliant and/or nonresponsive 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.

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 proposed KRCC 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 KRCC proposed).

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.

Does the proposed KRCC 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 KRCC 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?

Specific to this RFA: Will addressing the problems and critical barriers the project proposes to focus on result in a significant advancement of the concepts, methods, technologies, and/or approaches for both maternal and pediatric pharmacology? Will the resources and knowledges of the proposed KRCC improve scientific knowledge, technical capability, and enable maternal and pediatric therapeutics research and drug development? Does it have a strong focus on understanding disease heterogeneity and move towards precision medicine?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the proposed KRCC? 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 RFA: Is the plan for how all of the investigators will work across the proposed KRCC sufficient to assure cohesive interactions? Is there sufficient preliminary evidence the investigators can work together?

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?

Specific to this RFA: Will the proposed KRCC accelerate translational research across the spectrum of pediatric disease and maternal conditions?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the proposed KRCC? Have 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 proposed KRCC 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 RFA: Is the proposed infrastructure to facilitate broad data sharing adequate for a national resource? Are adequate mechanisms in place to ensure the coherence of the KRCC and maintain a multi-disciplinary focus while leveraging team science? Are appropriate, evaluative, and quantitative deliverables and milestones provided with clear metrics and plan for annual reprioritization? Will the proposed deliverables and milestones facilitate accomplishing the overall goals of the MPRINT Hub?

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?

Specific to this RFA: How well is the proposed KRCC integrated into other activities at the applicant's institution and does it leverage existing efforts in maternal and/or pediatric pharmacology? Is there strong commitment from the applicant's institution to support the proposed KRCC?

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.

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.

When the proposed KRCC 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.

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.

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.

Not Applicable

Not Applicable

Not Applicable

As applicable for the KRCC 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.

Not Applicable

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).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan.

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.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

As applicable for the KRCC proposed, reviewers will evaluate the following items while determining scientific and technical merit for the entire application, and in providing an impact score for the Knowledge Base and Portal but will not give separate scores for these items.

• Are the qualifications, experience, and commitment of the Project Lead and other personnel appropriate?
• Does the proposed Knowledge Base and Portal appropriately use publicly available data and current automated approaches to collect, analyze, and integrate relevant data?
• Will the proposed platform be able to identify knowledge deficits within maternal and pediatric pharmacology?
• Will the proposed web portal be user-friendly and enable users to explore, analyze, and visualize knowledge and predictions of drug metabolism, disposition, and response across the continuum of pediatric development and maternal conditions?
• Are appropriate strategies to support FAIR data principles as well as use of community standards for data and metadata, data identifiers, provenance of data, adequate infrastructure and storage described?
• Are adequate plans in place to work with the Pharmacometrics and Clinical Trial Design Core to develop metrics for data quality and utility for pharmacometrics modeling?
• Is the strategy to regularly monitor and evaluate usability of the system, including other components and sub-components of the MPRINT Hub, sufficient to allow evaluation and inform changes in implementation of the MPRINT Hub?
• Are appropriate, evaluative, and quantitative deliverables and milestones provided with clear metrics and plan for annual reprioritization?
• How well will the proposed deliverables and milestones facilitate accomplishing the overall goals of the MPRINT Hub?

As applicable for the KRCC proposed, reviewers will evaluate the following items while determining scientific and technical merit for the entire application, and in providing an impact score for the Pharmacometrics and Clinical Trial Design Core but will not give separate scores for these items.

• Are the qualifications, experience, and commitment of the Project Lead and other personnel appropriate?
• Will the Pharmacometrics and Clinical Trial Design Core serve as a national resource of highly experienced pharmacometricians to construct dynamic developmental models for drug distribution, metabolism, and response?
• Are the technical approaches proposed for the Pharmacometrics and Clinical Trial Design Core sufficient to serve as a framework to incorporate and deploy knowledge collected and aggregated by the Knowledge Base and Portal?
• Are the plans to begin to incorporate integration of individual-level genomic and other omics data and those with disabilities adequate?
• Are appropriate, evaluative, and quantitative deliverables and milestones provided with clear metrics and plan for annual reprioritization?
• How well will the proposed deliverables and milestones facilitate accomplishing the overall goals of the MPRINT Hub?

As applicable for the KRCC proposed, reviewers will evaluate the following items while determining scientific and technical merit for the entire application, and in providing an impact score for the Outreach, Dissemination, and Training Core but will not give separate scores for these items.

• Are the qualifications, experience, and commitment of the Project Lead and other personnel appropriate?
• Are the outreach, dissemination, and training objectives of the MPRINT KRCC appropriate for advancing the fields of maternal and pediatric therapeutics at a national level?
• Are the proposed plans to work across the MPRINT KRCC and with the MPRINT CETs adequate to assure a coordinated approach to outreach, dissemination, and training with a cohesive web and branding presence?
• Is the strategy to regularly monitor and evaluate how the MPRINT Hub, including its sub-components, is meeting the needs of the nation’s maternal and pediatric therapeutic research community sufficient?
• Are appropriate, evaluative, and quantitative deliverables and milestones provided with clear metrics and plan for annual reprioritization?
• How well will the proposed deliverables and milestones facilitate accomplishing the overall goals of the MPRINT Hub?

As applicable for the KRCC proposed, reviewers will evaluate the following items while determining scientific and technical merit for the entire application, and in providing an impact score for the Logistics Core but will not give separate scores for these items.

• Are the qualifications, experience, and commitment of the Project Lead and other personnel appropriate?
• Have the applicants provided evidence of their ability and plans to oversee and coordinate the proposed MPRINT KRCC?
• Do the plans of the Logistics Core adequately take in to account its roles in supporting a variety of meeting types, travel for its members and Extramural Program Consultants, and supporting all of the duties of the Steering Committee?
• Are the plans to solicit, review, select, and award the Opportunity Pool funds clear and appropriate?
• Are appropriate, evaluative, and quantitative deliverables and milestones provided with clear metrics and plan for annual reprioritization?
• How well will the proposed deliverables and milestones facilitate accomplishing the overall goals of the MPRINT Hub?

As applicable for the KRCC proposed, reviewers will evaluate the following items while determining scientific and technical merit for the entire application, and in providing an impact score for the Optional Core but will not give separate scores for these items.

• Are the qualifications, experience, and commitment of the Project Lead and other personnel appropriate?
• If implemented, will the Optional Core augment or enhance the capabilities of investigators using KRCC resources to enhance or create research within the MPRINT KRCC? Will the Optional Core be useful to the wider research community?
• Are the technical approaches proposed in the Optional Core appropriate?
• Are appropriate, evaluative, and quantitative deliverables and milestones provided with clear metrics and plan for annual reprioritization?
• How well will the proposed deliverables and milestones facilitate accomplishing the overall goals of the MPRINT Hub?

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by NICHD, 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:

• 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.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Child Health and Human Development (NACHHD) Council. 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.
• Evidence that the applicant and investigators are committed to policies as established by the SC including confidentiality, sharing of information and resources, cooperative interaction, and functioning as a national resource.
• Evidence of previous productive, cooperative, collaborative interaction.
• Assurance that there is approximately equal distribution of study between maternal pharmacology and pediatric pharmacology across the MPRINT Hub.

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.

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 grantee’s business official.

Awardees 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: Grantee 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 awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Awardee-selected Opportunity Pool projects require prior approval by NIH prior to initiation.

• The awardee institution will comply with the NIH Guidance on Changes That Involve Human Subjects in Active Awards and That Will Require Prior NIH Approval.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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.  This includes ensuring programs are accessible to persons with limited English proficiency. 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 http://www.hhs.gov/ocr/civilrights/understanding/section1557/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. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency.  Please 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 further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please 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.  Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. 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.
• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws.  Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions.  Please 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 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees 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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees 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.

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: GrantsInfo@nih.gov (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: support@grants.gov

Lesly-Anne Samedy-Bates, M.S., Pharm.D., Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-827-3241
Email: lesly-anne.samedy-bates@nih.gov

Sherry Dupere, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Telephone: 301-451-3415
Email: duperes@mail.nih.gov

Bryan Clark, MBA
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: clarkb1@mail.nih.gov

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.