Required Application Instructions

It is critical that applicants follow the 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

The R21 activity code 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. 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.

Applications for R21 awards should describe 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, will not be considered for R21 awards. Applications submitted to this FOA should be exploratory and novel. These studies should break new ground or extend previous discoveries toward new directions or application.

The purpose of this FOA is to stimulate investigations including translational, epidemiologic and clinical studies that improve the understanding, prevention and clinical outcomes of non-HIV infections transmitted from women to their offspring during pregnancy, labor/delivery, and breastfeeding. To improve the health and well-being of mothers, their infants, and families and cause a reduction in perinatal morbidity associated with infections, NICHD will support scientific research to increase the understanding of infectious diseases transmitted from mother to child.

The NICHD Maternal and Pediatric Infectious Disease Branch (MPIDB) organized a supplement published by the Journal of the Pediatric Infectious Disease Society (JPIDS) [September 2014] in which obstetrician and pediatric infectious disease experts were paired to author a review on the current status and research needs of selected perinatal infections.

High-priority perinatal infections of interest include, but are not limited to, cytomegalovirus, herpes simplex viruses, toxoplasmosis, viral hepatitis, Human T-cell lymphotropic viruses (HTLV-1/2), Trypanosoma cruzi (Chagas disease), enteroviruses and parvovirus B19.

Cytomegalovirus (CMV). CMV is the most common congenital viral infection, affecting up to 1% of infants. Mother to child transmission of CMV occurs transplacentally (congenital infection), during birth and through breast milk. Only congenital infection acquired antenatally is associated with disabilities which include hearing loss, mental retardation and neuromotor deficits. Cytomegalovirus perinatal transmission can occur if the mother was infected in the past through reactivation or becomes acutely infected during the current pregnancy. Trials are underway to evaluate whether CMV immunoglobulin given to women with primary CMV infection in pregnancy can prevent or mitigate the effects of congenital infection. Several drugs, including orally administered agents, are available with activity against CMV but these have not been fully evaluated for their ability to prevent or mitigate congenital infection when given to pregnant women. Further study is warranted to evaluate agents with activity against CMV for their ability to safely optimize neurodevelopmental and other outcomes in infants who have congenital infection.

Examples of relevant research topics include but are not limited to:

• Strategies to prevent primary CMV infection in a pregnant woman, including from offspring, intimate partner, or her occupational exposures (eg, day care center worker)
• Strategies to prevent transmission of CMV to the fetus after primary CMV infection in the mother
• Determination of the timeline for when and how women immune to CMV prior to conception transmit CMV to the fetus
• Development of novel, simple, rapid, feasible and cost-effective testing methods and/or strategies for primary CMV infection screening during pregnancy
• Development of novel, simple, rapid, feasible and cost-effective testing methods and/or strategies for primary CMV infection screening in the neonate

Herpes Simplex Viruses (HSV). Infections with herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) commonly cause genital infection, which, when acquired or reactivated during pregnancy, carry the risk of transmission to the fetus or neonate. Women who acquire primary or first-episode genital herpes during pregnancy are at greater risk for transmitting the infection than are women with recurrent genital herpes. Because viral infection and reactivation are frequently asymptomatic, many affected women are unaware of their infection and risk of transmission to their infants. Neonatal HSV infection can have devastating long-term consequences, especially when the central nervous system is involved. Treatment of affected neonates with intravenous acyclovir has improved outcomes, but requires prompt, accurate diagnosis and management and there is need for further improvement.

Examples of relevant topics of interest include but are not limited to:

• Determination of the effect of maternal suppressive antiviral therapy on the incidence of neonatal HSV infection
• Development of optimal treatment strategies for the management of HSV in discordant couples to prevent acquisition of HSV infection during pregnancy
• Development of novel, simple, rapid, feasible and cost-effective testing methods and/or strategies for peripartum HSV screening of asymptomatic women
• Development and safety testing of new or combinations of antiviral agents with increased efficacy, including enhanced central nervous system penetration and clinical outcomes for neonates with HSV infection
• Efficacy studies on preemptive antiviral therapy in neonates born to women symptomatically shedding HSV at the time of delivery

Congential Toxoplasmosis. Toxoplasma gondii is one of the most common parasitic infections in humans. Primary infection in a pregnant woman can cause severe and disabling disease in the developing fetus. Recent developments have included increased understanding of the role of parasite genotype in determining infectivity and disease severity. Risk factors for acquisition of infection have been better defined and the important role of foodborne transmission has been further delineated. In addition, strategies have emerged to decrease mother to child transmission through prompt identification of acutely infected pregnant women followed by appropriate treatment. Refined diagnostic tools, particularly the addition of IgG avidity testing, allow for more accurate timing of maternal infection and hence better decision making during pregnancy. Congenitally infected children can be treated, beginning in utero and continuing through the first year of life, to ameliorate the severity of disease. However, despite these many advances, better drugs, well defined strategies for screening of pregnant women, and improved diagnostic tests are still needed.

Examples of relevant topics in need of further research include but are not limited to studies of the:

• Distribution and role of toxoplasma genotypes in disease transmission and manifestation
• Development of feline vaccination for prevention of maternal infection
• Development of cost-effective screening strategies for pregnant women
• Development of improved diagnostic tools for maternal, fetal and infant infection
• Development of new medications to treat primary maternal infection
• Development and safety testing of better (less toxic; shorter) treatment regimens for infected fetuses and infants

Hepatitis B Virus (HBV). Mother-to-child transmission (MTCT) is responsible for more than one-third of estimated 360 million chronic HBV infections worldwide. An estimated 15-40% of persons chronically infected develop HBV-related complications, such as cirrhosis and hepatic carcinoma, and 25% die from these complications. MTCT can occur during pregnancy or during delivery. Screening pregnant women for HBV infection, maternal treatment with antivirals and providing infant post-exposure prophylaxis, are strategies for reducing MTCT transmission rates and the global burden of new chronic HBV infections. Administration of Hepatitis B Immune Globulin and hepatitis B vaccine within 24 hours of birth, followed by completion of the vaccine series is 85%-95% efficacious for prevention of MTCT. Despite timely post-exposure prophylaxis, however, MTCT occurs in 5-15% of infants. Hepatitis B surface antigen positive, hepatitis e antigen positive mothers with HBV DNA level 106 copies/mL (200,000 IU/mL) are at greatest risk of transmitting HBV to their infants. The safety and efficacy of antiviral drug use during pregnancy are areas of ongoing research. Attaining a better understanding of the mechanisms of MTCT, implementing existing policies on maternal screening and infant follow-up, and addressing research gaps, are critical for further reductions in MTCT transmission.

Examples of relevant topics of interest include but are not limited to studies that lead to the:

• Improvement in the understanding of the mechanisms of MTCT transmission prior to the intrapartum period
• Development of targeted approaches for prevention, including prevention during medically assisted reproduction
• Evaluation of mode of delivery in pregnant women with high-level HBV DNA, any added benefit from elective caesarean-section versus other types of delivery for the prevention of MTCT
• Determination of the indications, safety (mother and infant), efficacy, and timing for (eg, optimal HBV DNA level) antivirals in pregnancy
• Determination of the indications, safety and efficacy of antiviral prophylaxis for exposed newborn infants, to enhance or replace HBIG for the prevention of MTCT.

Hepatitis C virus (HCV). HCV is well known cause of chronic liver disease in adults, but the burden of HCV in pregnant women and children is underappreciated. HCV is estimated to affect 0.6 - 2.4% of all pregnancies with overall mother to infant transmission from 8 15%. The leading route of HCV acquisition in children is vertical transmission but the timing and mechanisms of transmission are not well understood. The rapid expansion of HCV treatment regimens free of interferon and ribavirin expand the therapeutic opportunities for pregnant women and children.

Examples of relevant topics of interest include but are not limited to studies that:

• Determine the timing of mother-child HCV transmission and principal host and viral factors that enhance or reduce perinatal HCV transmission risk.
• Determine the best way to reliably identify infected and uninfected infants in the first few months of life.
• Evaluate the safety (maternal, pregnancy and offspring outcomes) and pharmacokinetics of newer anti-HCV drugs in pregnancy.
• Evaluate the efficacy of newer anti-HCV drugs administered in pregnancy for treatment of maternal HCV and/or for prevention of infant HCV infection.
• Advance the understanding of predictors and mechanisms of spontaneous resolution of HCV viremia in infants
• Evaluate safety, PK and efficacy of newer anti-HCV drugs in infants to prevent or treat chronic infection.

Human T-cell lymphotropic viruses (HTLV). HTLV-1 and HTLV-2 are retrovirus infections with a worldwide distribution and high regional variation in prevalence rates that reach 5-30% of the population in endemic areas (eg, Japan, Caribbean and South America for HTLV-1). It is estimated that approximately 20 million people worldwide are infected with HTLV-1/2. HTLV-1 is linked to malignant neoplasms (e.g. leukemia, lymphoma) and neurologic disorders (e.g. tropical spastic paraparesis) while the linkage of HTLV-2 to neurologic and other problems is weaker. Perinatal transmission of HTLV-1/2 is thought to occur primarily during breastfeeding. The spectrum of clinical consequences of HTLV 1-2 infection in pregnant/breastfeeding women and their infants is not fully understood. There are no effective drugs to prevent or treat HTLV 1-2 infection.

Examples of relevant research questions include but are not limited to studies that:

• Determine what viral , host , and environmental factors are important in mother to child transmission of HTLV.
• Determine to what extent mother to child transmission occurs during pregnancy and labor/delivery
• Determine the transmission rates of HTLV using different modes of delivery.
• Determine if anti-retroviral drugs (testing existing drugs for safety and efficacy as well as new drugs) are effective in lowering HTLV transmission in the perinatal period or improving outcomes for infected infants

Trypanosoma cruzi (Chagas disease). Chagas disease is vector-borne, endemic to South and Central America and Mexico, and is among the world’s most neglected tropical diseases. Due to population migration, T. cruzi is increasingly becoming a public health problem in non-endemic settings, such as the United States. Success with vector control strategies has led to a relative increase in the burden attributable to congenital transmission of T. cruzi. In T. cruzi endemic settings, approximately 5% of infected pregnant women transmit to their offspring. Congenital T. cruzi infection is generally asymptomatic and parasitological and serological testing is required for diagnosis.

Relevant research gaps include but are not limited to the need to:

• Evaluate new strategies to improve follow up and treatment of congenital infection with existing therapies
• Develop new diagnostic tests with high validity and reliability for timely detection of congenital and maternal T. cruzi infection
• Develop treatment during preconception and pregnancy to reduce congenital transmission
• Develop new drugs with shorter treatment courses and fewer side effects
• Establish routine surveillance and monitoring of congenital T. cruzi in endemic and non-endemic settings
• Understand maternal, fetal, and parasitic characteristics that may contribute to transmission and clinical symptoms
• Characterize mechanisms for congenital transmission during pregnancy, delivery, and lactation
• Evaluate the relation between maternal T. cruzi infection and fetal and neonatal immune health
• Determine the impact of pregnancy on the natural history of T. cruzi infection and characteristics affecting prognosis
• Estimate burden and role of re-infection and multi-strain infection on congenital transmission

Assess the impact of vector control on maternal parasitic load and congenital transmission

For other non- HIV infectious diseases including Parvovirus, enterovirus and other pathogens the timing, mechanisms, and risk factors that underlie perinatal infection are incompletely understood.

Relevant research gaps include but are not limited to the need for:

• Well-designed studies that use epidemiologic, laboratory and/or clinical methods to elucidate the interaction of pathogen with host, maternal and fetal/infant and other factors that can enable or impede infection transmission.
• Development of novel methods, targets and strategies for rapid, point of care screening and diagnosis of perinatally transmitted infections, including maternal, fetal, placental and/or infant testing, that are cost-effective and can be used for simultaneous testing for multiple infections of interest.
• Studies of safety, pharmacokinetics and/or efficacy to evaluate drugs and other agents with promise for prevention or treatment of perinatally transmitted infections but for which only in vitro, animal and/or non-pregnant human (beyond infancy) data may exist;
• Studies testing the ability of such drugs and other agents to reduce risk of perinatal infection
• Studies to evaluate improved outcomes maternal, pregnancy and infant in the face of infection.

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).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the 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 Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

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

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 I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

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 our Post Submission Application Materials policy.

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

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? 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? 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?

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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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.

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 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 appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

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.

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.

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.

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://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 CenterTelephone: 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

Nahida Chakhtoura, MD, MsGH (Obstetrics)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6872
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: 301-435-6975
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.

Department of Health
and Human Services (HHS)