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

Purpose/Research Objectives

The NICHD Exploratory/Developmental Grant program supports exploratory and developmental research projects that fall within the NICHD mission by providing support for the early and conceptual stages of these projects. These studies may involve considerable risk but may lead to a breakthrough in a particular area, or to the development of novel techniques, agents, methodologies, models, or applications that could have a major impact on a field of biomedical, behavioral, or clinical research.

The evolution and vitality of the biomedical, behavioral, and clinical sciences require a constant infusion of new ideas, techniques, and points of view. These may differ substantially from current thinking or practice and may not yet be supported by substantial preliminary data. Through the NICHD Exploratory/Developmental Research Grant Program, the NIH seeks to foster the introduction of novel scientific ideas, model systems, tools, agents, targets, and technologies that have the potential to substantially advance biomedical, behavioral, and clinical research within the NICHD scientific mission.

This program is intended to encourage new exploratory and developmental research projects. For example, such projects could assess the feasibility of a novel area of investigation or a new experimental system that has the potential to enhance health-related research. Another example could include the unique and innovative use of an existing methodology to explore a new scientific area.

Specific Areas of Research Interest

Areas of research covered by the proposed R21 projects must fall within the scientific missions of the twelve Scientific Branches of the NICHD Division of Extramural Research (DER) or the National Center for Medical Rehabilitation Research (NCMRR). Details about those scientific missions and program staff contacts may be found on the web pages for the DER scientific branches at: http://www.nichd.nih.gov/about/org/der/branches/Pages/index.aspx and the NCMRR at: http://www.nichd.nih.gov/about/org/ncmrr/Pages/overview.aspx. Specific research priorities of DER branches and NCMRR are listed as follows.

This FOA will not support clinical trials.

The Child Development and Behavior Branch (CDBB) mission is to support research focused on neurobiological, genetic, environmental, or social factors impacting developmental processes associated with behavior, cognition, learning (including reading, math and science learning and related disabilities), language, motor or social-emotional functioning or health status of infants, children, and young adults.

CDBB high priority research areas include but are not limited to the following topics:

• Bilingual and biliteracy development?
• Measures of neurodevelopment
• Pediatric primary care behavioral and health promotion interventions
• Psychosocial adjustment for individuals in high-risk environments
• School readiness skills in economically and socially disadvantaged children
• Reading, writing, and mathematics
• Reasoning

CDBB low priority research areas for the R21 mechanism include:

• Human or animal model research focusing on a specific disease, organ system or disability that lacks a developmental focus or does not address underlying developmental processes.
• CDBB supports primarily mammalian animal models and will not accept avian models if focused solely on vocal learning or language development and does not have a specific cognitive or brain development focus. Invertebrate models are not accepted.
• Research using animal models to study maternal behavior without a specific focus on brain, immunologic, or neuroendocrine factors impacting maternal or offspring behavior or without a focus on mechanisms underlying offspring cognition, brain development or health.
• Research investigating factors affecting child or adolescent self- and/or peer management of chronic conditions.
• Research focusing primarily on professional development training of teachers or administrative personnel at the elementary school level or above.
• Research on couples relationship education, relationship/marriage therapy, or interventions related to couples relationship quality, marriage, or divorce.
• Couple therapy for infertility.

The Contraception Research Branch (CRB) mission is to develop and support research and research training programs in contraceptive discovery and development. Major research areas include studies of: new contraceptive methods; mechanisms of action and effects of contraceptive and reproductive hormones, drugs, devices, and procedures as well as optimal formulations and dosages of contraceptive agents.

CRB high priority research areas include but are not limited to the following topics:

• Developing new methods to deliver pharmacologic agents to the sites of gamete production, maturation, and/or function.
• Developing methods that prevent both fertility and the transmission of sexually transmitted infections.
• Comprehensive identification, characterization and/or validation of potential non-steroidal male and female contraceptive targets.
• Developing more efficient and/or predictive strategies or methods to validate potential contraceptive targets.
• Characterizing testicular stem cells to identify targets for male contraception.
• Elucidating the mechanism of transport of drugs and/or drug like molecules across the blood-testis and/or blood-epididymal barrier(s).

CRB low priority research areas for the R21 mechanism:

• Basic biological research with no reference or immediate relevance to contraceptive use or contraceptive method development.
• Research to use, develop, or test methods that utilize chemicals known to have toxic properties.
• Research to develop contraceptive methods which propose the use of chemicals which cannot be developed into contraceptive methods due to existing intellectual property considerations.

The Developmental Biology and Structural Variation Branch (DBSVB) mission is to support research focused on understanding the biological processes controlling normal embryonic development as well as the mechanisms underlying the susceptibility and etiology of structural birth defects. Major program areas in the Branch include developmental genetics; systems developmental biology; early embryonic development and differentiation; biophysics/biomechanics of development; developmental neurobiology and neural crest differentiation; organogenesis; in vivo mechanisms of tissue/organ regeneration; stem cells and iPSCs; and structural birth defects.

DBSVB high priority research areas include but are not limited to the following topics:

• Novel, exploratory/developmental projects of high potential significance relevant to the research areas described in the Branch description [see website]
• Developing tools or new animal models for studying embryonic development or structural birth defects
• Projects using stem cells or iPSCs for understanding human embryonic development and birth defects
• Projects addressing the emerging area of developmental metabolomics as related to embryonic processes or the etiology of structural birth defects

DBSVB low priority research areas for the R21 mechanism:

• Basic cell biology and molecular biology projects addressing basic cellular processes that are not specifically related to embryonic development, such as cell cycle control, organelle biogenesis, membrane structure and function, protein processing, DNA replication, damage and repair, etc.
• Projects using stem cells or iPSCs to study disease in adults
• Developing plants or unicellular organisms, such as bacteria, archaea, protozoa, unicellular algae, and unicellular fungi

The Fertility and Infertility Branch (FIB) mission is to support research aimed at alleviating infertility, uncovering new pathways to control fertility, and expanding our fundamental understanding of processes that underlie human reproduction. The interests of the branch include basic research that increases our knowledge base regarding fertility regulation and applying that knowledge to develop more effective strategies for the diagnosis, management and prevention of human conditions that compromise fertility, with the ultimate goal of promoting a better quality of life for all individuals.

FIB high priority research areas include but are not limited to the following topics:

• Studies of gamete quality and pre-placental processes as they relate to the etiology of early pregnancy loss.
• Studies on transgenerational epigenetic inheritance.
• Studies to investigate the relationship of fertility status to overall health and disease.
• Genetic basis of idiopathic male and female fertility.
• Impact of nutrition and metabolism on fertility.
• Identification of biomarkers to study reproductive transitions.
• Development of innovative technologies and model systems that can advance progress in reproductive biology and medicine.

FIB low priority research areas for the R21 mechanism:

• Basic biology of meiosis with no reference or immediate relevance to fertility or reproduction.
• Cellular mechanisms of epigenetic regulation with no reference or immediate relevance to a reproductive phenotype or function.
• Biology of ovarian and testicular cancer.
• Male urogenital tract studies with a specific focus on urology.
• Non-mammalian models of uterine function.
• Examination of neuroendocrine signaling cascades in isolation from networks. couple therapy for infertility.

The Gynecologic Health and Disease Branch (GHDB) mission is to support research related to gynecologic health throughout the reproductive lifespan. The GHDB portfolio includes studies on endometriosis, adenomyosis, uterine fibroids, gynecologic pain syndromes (chronic pelvic pain, vulvodynia, and dysmenorrhea), and pelvic floor disorders.

GHDB high priority research areas include but are not limited to the following topics:

• Research involving longitudinal studies that include relevant gynecologic questions.
• Delineating the genetic, cellular, molecular, environmental, and psychosocial factors underlying the etiology of chronic gynecologic pain syndromes.
• Developing novel, non-hormonal pharmacologic treatments for gynecologic disorders.
• Developing novel imaging methods and biomarkers for gynecologic disorders.
• Investigating the genome, epigenome, and/or transcriptome as they impact development, progression, and/or treatment response in gynecologic conditions.
• Investigating the role of endogenous stem cells in the etiology or treatment of gynecologic disorders.
• Transdisciplinary research based on findings from diverse fields to advance basic and mechanistic understanding of gynecologic health and disease.

GHDB low priority research areas for the R21 mechanism:

• Studies focusing on interstitial cystitis, irritable bowel syndrome, incontinence (fecal or urinary) or sexual dysfunction due to causes other than pelvic floor disorders.
• Research on general pain mechanisms or treatments that use female gynecologic pain only as a model, rather than more tailored approaches.
• Studies investigating interventions for gynecologic disorders that are within the mission of other Institutes or Centers, such as alternative/complementary or cognitive behavioral therapies.

The Intellectual and Developmental Disabilities Branch (IDDB) mission is to support research that will improve the understanding, screening, and treatment of conditions associated with intellectual and developmental disabilities, including common and rare neuromuscular and neurodevelopmental disorders.

IDDB high priority research areas include but are not limited to the following topics:

• Interdisciplinary studies emphasizing the cellular, genetic, epigenetic, and environmental factors that contribute to the cognitive and behavioral manifestations of IDD, including (but not limited to) Down, Fragile X, and Rett syndromes, inborn errors of metabolism, and autism spectrum disorders.
• Research on one or more comorbid conditions of IDD, including but not limited to: disordered sleep, self-injurious behaviors, obesity, gastrointestinal dysfunction, seizures/epilepsy, attention deficit/hyperactivity disorder, anxiety, depression, psychosis, and other mental health disorders.
• Research on the development and/or implementation of new screening tests for the prenatal, newborn, and early childhood periods that assesses the efficiency and effectiveness of translating these tools into clinical care and the community setting.
• Research establishing the validity of biomarkers and outcome measures for IDD symptoms, severity assessments, and treatments, especially outcomes targeting cognitive (including language), behavioral (adaptive or maladaptive), social, and medical issues.
• Research examining transitional time periods of particular interest for IDD, including presymptomatic, adolescent to adulthood, middle adulthood to aging (prevalence of dementia in IDD populations), and causes of mortality in IDD.
• Developing, disseminating, and implementing treatments for IDD that will impact clinical care and improve quality of life, including physiological, cognitive and behavioral manifestations, for those with IDD conditions.?

IDDB low priority research areas for the R21 mechanism:

• Research that focuses on parent or family outcomes rather than outcomes of the individual with IDD.
• Research that focuses on fundamental mechanisms of genes with tangential relationship to IDD conditions.

The Maternal and Pediatric Infectious Disease Branch (MPIDB) mission is to support and conduct domestic and international research related to the epidemiology, diagnosis, clinical manifestations, pathogenesis, transmission, treatment, and prevention of HIV infection and its complications in infant, children, adolescents, and women (pregnant and non-pregnant), as well as HIV-associated co-infections (such as tuberculosis, hepatitis, and malaria) in children and pregnant women. MPIDB also supports and conducts research on other significant infectious diseases, including: congenital infections, such as Zika virus and cytomegalovirus; tropical diseases, specifically those that affect children and pregnant women; emerging and re-emerging infectious diseases; and vaccine-preventable disease in infants, children, adolescents, and pregnant women. ?

MPIDB high priority research areas include but are not limited to the following topics:

• HIV: Cure/remission and reservoirs in infants and children.
• HIV: Prevention strategies in adolescents, including uptake of and adherence to HIV prevention modalities.
• HIV: Adverse pregnancy and infant outcomes.
• Emerging and re-emerging infectious diseases.
• Impact of infections on developing nervous system.
• Understanding of the immune connection and communication between the pregnant women, placenta, and fetus, and the effects on infant immunity.

MPIDB low priority research areas for the R21 mechanism:

• Basic biomedical research focused on neurocognitive dysfunction in HIV/AIDS.
• Research applications on HIV and other infectious diseases where the focus and/or impact on infants, children, adolescents, and pregnant women represent only a minority of the work proposed.
• Research with multiple behavioral and/or biological outcomes that are of relevance to HIV (and/or specified infectious disease), where HIV (and/or the specified infectious disease) is not the focus.

The Obstetric and Pediatric Pharmacology and Therapeutics Branch (OPPTB) mission is to support basic, translational, and clinical research to improve the safety and efficacy of therapeutics, primarily pharmaceuticals, and to ensure centralization and coordination of research, clinical trials, and drug development activities for obstetric and pediatric populations. Implementation of the Best Pharmaceuticals for Children Act (BPCA) activities at the NICHD is among the major activities for the Branch.

OPPTB high priority research areas include but are not limited to the following topics:

• Developmental pharmacology and pathophysiology of pregnancy.
• New drug development and drug repurposing.
• Novel alternative designs for pediatric and obstetric clinical trials.
• Outcome measures and biomarkers for pediatric and obstetric clinical trials.
• Pediatric formulations.
• Therapeutic devices.
• Developmental pharmacogenomics, toxicogenomics and epigenomics.
• Pk, safety and efficacy of pharmaceuticals in pregnant/obese pregnant teenagers.

OPPTB low priority research areas for the R21 mechanism:

• Pediatric cancer and pediatric cancer medication development is not within the priorities of our branch. Applications in those areas should be directed to the National Cancer Institute unless they address information that can be generalized for non-cancerous conditions, e.g. identification of biomarkers that can be applied to non-cancerous conditions as well.
• Diseases, disorders or conditions that are within the research mission of another NIH Institute/Center, unless information from the study can be applied directly to pediatric or obstetric populations.

The Pediatric Growth and Nutrition Branch (PGNB) mission is to support research on how nutrition promotes healthy growth and development; lactation and breastfeeding, including the interactions of breast milk and the microbiome, as well as the effects of breast milk's non-nutritive compounds (e.g., oligosaccharides and dipeptides) on enteric pathogens; the causes of obesity in childhood and sequelae of childhood obesity in adulthood; the genetic, nutritional, and hormonal antecedents of bone health and the origins of osteoporosis; the neuroendocrine basis of growth and the onset of puberty; and the development of the hypothalamo-pituitary adrenal, gonadal, and thyroid axes.?

PGNB high priority research areas include but are not limited to the following topics:

• Interaction of nutrients and the microbiome
• Antimicrobial activity of breast milk
• Attainment of peak bone mass and peak bone strength

PGNB low priority research areas for the R21 mechanism:

• Influence of physical environment on weight loss

The Pediatric Trauma and Critical Illness Branch (PTCIB) mission is to support research focused on preventing, treating, and reducing all forms of childhood trauma, injury, and critical illness to enhance healthy outcomes across the continuum of care. Please see Advances in Pediatric Trauma and Critical Illness Research: BUILDING THE FIELD ADVANCING THE SCIENCE, Action Agenda.

PTCIB high priority research areas include but are not limited to the following topics:

• Pediatric critical care medicine, epidemiology, pathophysiology, prevention and management of critical illness.
• Ethical, translational, and applied research in pediatric critical care practice.
• Injury prevention, trauma and emergency care.
• Psychological trauma, traumatic stress, violence and violence-related injury and child maltreatment.

PTCIB low priority research areas for the R21 mechanism:

• Studies of adolescent behavioral outcomes or developmental trajectories of post-injury outcomes.
• Research on bullying, teen dating violence or interpersonal processes.
• Studies in which the preponderance of the science is focused on child developmental/parenting processes and outcomes.
• Studies examining mental illness or psychopathology as primary outcomes.
• Studies in which the primary aim is understanding the pathophysiology of PTSD.
• Studies focused on chronic conditions unless the primary aim of the science is on treatment in the PICU or the prevention of a chronic condition from progressing to a critical illness.
• Projects in which critical care is provided exclusively in the NICU.
• Studies of treatment in the emergency department that are not related to trauma or to severe, potentially life-threatening illness.
• Studies of chronic/long-term rehabilitation or rehabilitation related to a chronic condition.

The Population Dynamics Branch (PDB) mission is to support research and data collection in three areas: demography the scientific statistical study of human populations; population health research on human health, productivity, behavior, and development at the population level, using population representative samples or policy or natural experiments; and behavioral and social science research on reproductive health.

PDB high priority research areas include but are not limited to the following topics:

• Behavioral research on the use and non-use of contraception.
• Health and disease across the lifespan.
• Multi-level interactions and inputs to human health and development, including gene x environment interactions.

PDB low priority research areas for the R21 mechanism:

• Relationship education, relationship/marriage therapy, or interventions related to relationship quality, marriage, or divorce.
• Couples communication except as it is related to unintended pregnancy, contraception, HIV/AIDS, and other sexually transmitted infections.
• Couple therapy for infertility
• Attitudes towards hypothetical contraceptive method(s).
• Medical interventions except those related to reproductive health.
• Secondary analysis of quantitative data from non-representative samples.
• Collecting quantitative and qualitative data based on non-representative samples except as a feasibility study leading to population-representative data collection.

The Pregnancy and Perinatology Branch (PPB) mission is to support research to improve the health of women before, during, and after pregnancy, improve pregnancy outcomes and increase infant survival free from disease and disability.

PPB high priority research areas include but are not limited to the following topics:

• Improving the health of women before, during and after pregnancy.
• Improving pregnancy outcomes.

PPB low priority research areas for the R21 mechanism:

• Management of maternal behavioral dysfunction and psychiatric disorders; neurobiology of repair and regeneration during development; developmental immunology.

The National Center for Medical Rehabilitation Research (NCMRR) mission is to foster development of scientific knowledge needed to enhance the health, productivity, independence, and quality-of-life of people with physical disabilities.

NCMRR high priority research areas include but are not limited to the following topics:

• Multimodal approaches promoting plasticity and sensorimotor function, particularly the combination of physical therapy with regenerative, pharmacological, or stimulation treatments.
• Developing objective measures and biomarkers that may predict rehabilitation treatment response, monitor functional progress, and tailor interventions to the individual abilities, needs, and resources of the person with disabilities.
• Developing scalable strategies and technologies to monitor outcomes in real-world settings (e.g., home, community, workplace and school). This approach includes the use of engineering and social-science to understand environmental supports and barriers, monitor individual participation, understand health service access, and support health and independence.
• Identifying, preventing, and treating key secondary conditions that are associated with physical impairments and disabilities.
• Addressing key lifespan transitional issues, such as the physical and developmental transition from adolescence to early adulthood and functional independence.

NCMRR low priority research areas for the R21 mechanism:

• Studies focused primarily on pathophysiology.
• Continued development/refinement of existing technologies.
• Development of animal models.

Applications for Exploratory/Developmental Research Grant awards should include projects distinct from those supported through the traditional R01 activity code. For example, long-term projects, or projects designed to increase knowledge in a well-established area, are not appropriate for this FOA. Applications submitted to this FOA should be exploratory and novel. These studies should break new ground or extend previous discoveries toward new directions or applications. Projects of limited cost or scope that use widely accepted approaches and methods within well-established fields are better suited for the NIH Small Research Grant Program.

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 in response to 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)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• 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) (formerly CCR) 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

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

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

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

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, should address a Data Sharing Plan.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Form only available in FORMS-E application packages for use with due dates on or after January 25, 2018.

When involving NIH-defined human subjects research, clinical research, and/or 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: All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

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

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

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

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

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

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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. See Section III of this FOA for information on registration requirements.

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. 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

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

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

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

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

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 project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

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

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?

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

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

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?

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 six 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 six 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 project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children 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.

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

Not Applicable

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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

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

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 (GDS).

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.

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of review by the National Advisory Child Health and Human Development 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 NICHD program priorities.
• Relevance of the proposed project to the scientific missions and research priorities of the DER Branches or the NCMRR.

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.

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 law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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. HHS provides general 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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. 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. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. 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 http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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 progress report, 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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

NICHD Referral Office
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Email: [email protected]

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

Bryan S. Clark, MBA
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-402-0915
Email: [email protected]

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.