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

The purpose of this funding opportunity announcement (FOA) is to support and facilitate multidisciplinary research approaches for the development of novel nonsteroidal contraceptive products for men and women that act prior to fertilization. This FOA aims to position innovative and validated methods for future clinical development.

Background

Nearly half of all pregnancies in the United States are unintended. There is a critical need for fertility regulation methods that fit the needs of women and men throughout their reproductive lives. This FOA supports the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) in its mission to develop novel, safe and effective contraceptive methods for men and women.

An important component of any early stage product development project is to conduct the necessary research to demonstrate that if the proposed modulation is successful (e.g., inhibition of a specific enzyme), the desired result will be achieved (e.g., infertility). This is commonly referred to as "validation". When a specific and defined molecule is targeted for modulation (e.g., inhibition of a specific enzyme), the specific molecule is referred to as a "target" and the validation process is referred to as "target validation". If more than one specific molecule is targeted (e.g., two related enzymes), the same principals apply for the two molecules (i.e. demonstration that a well characterized modulation of both molecules will achieve the desired result). In addition to supporting contraceptive development research on validated modulations, this FOA supports early stage, high-risk projects lacking validation by allowing validation during the R61 phase.

Phased Innovation Awards

This funding opportunity will use the R61/R33 phased award mechanism. Support will be provided for

up to two years for the R61 phase, and up to three years of support may follow for the R33 phase.

No less than two months before the completion of the R61 phase, awardees may submit the R33 transition package, which includes the R61 progress report describing in detail the progress towards the R61 milestones, and a description of how research proposed for the R33 phase will be supported by the completion of the R61 phase milestones. These materials will be evaluated by NIH Program staff. R33 funding decisions will be based on the original R61/R33 peer review recommendations, successful completion of transition milestones, Program priorities, and availability of funds. Grants receiving a positive R33 funding decision will be transitioned to an R33 award without the need to submit a new application. It is anticipated that not all R61 awardees will be transitioned into the R33 phase. Applicants must be aware that use of a no-cost extension at the end of the R61 period could jeopardize the award of the R33.

Validation

The purpose of validation is to provide evidence that if the proposed research project is successful in achieving the modulation outlined in the application, the contraceptive method will be effective. Validation, as defined in this FOA, is the demonstration in a mammalian species that the modulation proposed in the application to achieve a contraceptive effect, whether specific (e.g. antagonism of a single specific enzyme) or non-specific (e.g., sperm motility inhibition by exposure to a high molecular weight polymer) results in infertility. Reversibility does not need to be demonstrated as part of the validation process.

Subfertility is not sufficient to constitute validation. Subfertility as defined in this FOA, is the generation of live animals from in vivo mating trials and/or an in vivo or in vitro fertilization rate greater than zero.

• Validation is not required for applications focused on the development of devices for the delivery of nonsteroidal contraceptive agents.

If the application proposes a modulation to achieve contraceptive effect that is not validated, the milestones in the R61 phase must include a validation plan, including one or more milestones that address the outcome of the validation studies. Validation of the proposed modulation to achieve contraceptive effect by the completion of the first phase is required for transition to the R33 phase.

Examples of research projects and acceptable forms of validation

For applications focused on modulation of defined molecular targets:

Proposed contraception research projects focused on the modulation of specific molecular interaction between an administered molecule (e.g., chemical, antibody) and a defined molecular target(s) (e.g., enzyme, transporter, ion channel) to achieve modulation of the target (e.g., agonism, antagonism) leading to a contraceptive effect (i.e., infertility).

• Examples include but are not limited to:
• Targeted deletion of the gene encoding the target to be modulated, resulting in infertility
• Development of an antibody that binds specifically to the target and inhibits fertility in a concentration dependent manner in a relevant model (e.g., in vitro fertilization).
• Specific inhibition of RNA corresponding to target to be modulated leading to inhibition of gametogenesis or loss of gamete function as demonstrated by histology, mating studies or in vitro fertilization.
• For high molecular weight polymers:

It is generally accepted that natural or synthetic high molecular weight polymers that interact with cells and inhibit transport (e.g., sperm motility) act via multiple non-specific binding events. Validation of these molecules requires (1) supporting evidence that their action is mediated by non-specific binding, (2) demonstration that the agent can achieve a contraceptive effect, and (3) lack of toxicity at or above the dose and duration of contact expected to be used to achieve contraceptive effect in a relevant model.

• Examples include but are not limited to:
• Use of the agent in a mammalian animal model resulting in infertility;
• Use of the agent to inhibit sperm motility in vitro to a level consistent with infertility at concentrations consistent with expected in vivo use;
• Use of the agent to inhibit in vitro fertilization when the product is at concentrations consistent with in vivo use.

For low weight molecules with contraceptive properties that act via unknown molecular interactions:

For low molecular weight molecules (<2000 Daltons) with contraceptive properties that do not have an identified mechanism of action, validation must include demonstration (1) that the compound can achieve a reversible contraceptive effect in a relevant model, and (2) a lack of toxicity at the dose and duration of dosing used to demonstrate a reversible contraceptive effect.

• Examples include but are not limited to:
• Mating studies demonstrating a reversible contraceptive effect in all animals at a defined dose/duration, including pharmacokinetic analysis;
• Toxicological assessment demonstrating a lack of toxicity at the dose/duration resulting in a reversible contraceptive effect in all animals.

For projects focused on the development or improvement of vehicles for delivery of nonsteroidal contraceptive agents.

• Validation is not required for vehicles for the delivery of nonsteroidal contraceptive agents.

Research Scope

The purpose of this announcement is to support and facilitate multidisciplinary research approaches to the development of novel nonsteroidal contraceptive methods for men and women that act prior to fertilization, including small molecules, large molecules, biologics and medical devices. This FOA supports research on pre-clinical stages of development from target validation through IND-enabling studies. This FOA also supports the development of multi-purpose prevention technologies with both contraceptive and anti-infective properties.

Contraception Development Research Projects appropriate for this FOA include, but are not limited to the following:

Male or female contraceptive development based on nonsteroidal action;

Male and/or female pre-coital on-demand contraception based on nonsteroidal action;

Nonsteroidal multipurpose prevention technology (MPT) products based on nonsteroidal action with both contraceptive and anti-infective properties;

Development or improvement of vehicles for delivery of nonsteroidal contraceptive agents, including but not limited to vaginal films and microneedles.

Applications focused in the following areas are considered not responsive and will not be reviewed:

• Applications based on mechanisms of contraceptive action that may act post-fertilization
• Applications that focus on the development of methods that may act via the oviduct or uterus
• Applications based on intrauterine devices/intrauterine systems
• Applications for the development of molecules for male or female contraception that act via steroid receptors.
• Applications for the development of contraceptive methods that require the administration of one or more exogenous steroidal molecules that act via nuclear steroid receptors
• Applications not focused on the development of a contraceptive product or delivery system
• Applications that propose clinical trials
• Applications focused on the development of a contraceptive method/product that acts by total physical obstruction of any region/segment of the male or female reproductive tract
• Applications focused on male or female condom development
• Applications focused on target identification, unless they are to identify the target of a low molecular weight molecule with contraceptive properties that act via an unknown molecular interaction
• Applications for the development of the following molecules and/or their chemical derivatives;
• Gamendazole
• H2-Gamendazole
• Adjudin
• Gossypol
• alpha-chlorohydrin
• Applications based on the following class of targets:
• Vitamin receptors
• Applications focused on the development of type I-II kinase inhibitors
• Application focused on the development of molecules or devices that disrupt/perturb the blood-testis and/or blood-epididymal barriers
• Applications focused on molecular targets for which there is no human ortholog
• Applications that do not provide a clear path to transition from the R61 to the R33 phase of the award

Additionally, the following applications will not be reviewed:

• Applications proposing only the R61 mechanism, or only the R33 mechanism
• Applications that do not provide milestones for the transition from the R61 to the R33 phase of the award (see Section IV.2)

Milestones

It is expected that proposed milestones will be quantitative in nature and unique for each project depending on its position within the development process. The following are example categories to be developed into quantitative milestones.

I. Validated Projects: Examples of scientific studies to be developed into quantitative milestones to be completed in the R61 phase may include;

• High Throughput screening
• Compound optimization
• Demonstration of target/compound interaction
• In vivo mating studies
• IND-enabling studies

II. Projects with a defined molecular target lacking validation: Examples of scientific studies to be developed into quantitative milestones to be completed in the R61 phase may include;

• Validation
• Assay development
• High throughput screening

III. Non-validated low molecular weight compounds (<2000 Daltons): Examples of scientific studies to be developed into quantitative milestones to be completed in the R61 phase may include;

• Mating studies
• Pharmacokinetic studies at doses that cause reversible contraception
• Toxicology studies

IV. For projects focused on the development or improvement of vehicles for delivery of nonsteroidal contraceptive agents. Examples of scientific studies to be developed into quantitative milestones to be completed in the R61 phase may include;

• Mating studies using the delivery system to delivery contraceptive agent
• Pharmacokinetic studies
• Studies to evaluate the local effects of the delivery system (e.g., inflammation)

Subcontracting of Research Facilities

PDs/PIs may sub-contract portions of their research they are not able to conduct at their facility or institute to outside vendors (e.g., animal studies, protein production, high throughput screening, medicinal chemistry and x-ray crystallography). Applicants interested in subcontracting facilities must obtain agreement in advance, provide for the services in the budget, and include a letter of support in the application (see Section IV.2). Applicants who desire assistance in identifying subcontractors for animal studies or drug development services are advised to consult the NICHD Scientific/Research contact.

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

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

Higher Education Institutions

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

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o 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, 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.

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

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

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

The letter of intent must be sent to:

Daniel S. Johnston, PhD
Telephone: 301-827-4663
Email: [email protected]

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.

Facilities and Other Resources

If a subcontractor is proposed, provide relevant details on the subcontractor's research environment.

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:

Specific Aims: The specific aims for both the R61 phase and the R33 phase must be included in the

Specific Aims attachment. Include headers indicating the R61 specific aims and the R33 specific aims.

Research Strategy: Applicants must provide an overview of the proposed research, including milestones, feasibility, and timelines for completion of both phases. In preparing the R61/R33 application, investigators must consider that the application will be assigned a single overall impact score. Thus, clarity and completeness of the application regarding specific goals and the feasibility of each phase and the Transition Milestones are critical. Applicants must provide separate sections to describe the R61 and R33 phases, as appropriate. Applicants must not repeat information or details in the R33 section that are described in the R61 section unless they differ substantially.

The Research Strategy must include:

• A description of the validation status of the project at the time of submission.
• For applications focused on development of a treatment containing two or more identified molecules, potential compound interactions (i.e., drug:drug interactions) must be addressed.
• For non-validated projects, a validation plan must be proposed in the R61 phase.
• A comprehensive Gantt chart must be provided for each phase outlining the proposed research and incorporating all proposed milestones.
• For projects that are in or have completed the chemical optimization phase, describe potential routes of delivery/administration.
• For multi-purpose prevention projects, discuss the anti-infective strategy, the proposed delivery method and the potential impact on public health.
• Applicants must include a section titled, "Transition Milestones for the R61 Phase." This section must be placed at the end of the R61 section within the Research Strategy. In this section, applicants must propose milestones for completion of the R61 phase of the project, including:
• A discussion of the suitability of the proposed milestones for assessing success in the R61 phase,
• A discussion of the implications of successful completion of these milestones for the proposed R33 phase.
• All milestones must be specific, quantifiable and scientifically justified; they must not be a simple restatement of the R61 phase specific aims.
• The milestones must include go/no-go criteria integrated into the milestone criteria.
• The proposed Transition Milestones must be sufficiently rigorous scientifically to be valid for assessing progress in the R61 phase.
• For non-validated projects, the section titled "Transition Milestones for the R61 Phase" must include one or more quantitative milestones for completing validation studies.

Letters of Support: Letters of support must be provided for all collaborators and subcontractors

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, must include a Data Sharing Plan. The Data Sharing Plan will be considered during peer review and by program staff as award decisions are being made as appropriate and consistent with achieving the goals of the program. It is expected that the results of NICHD-funded research will be shared with the wider scientific community in a timely manner.

Awardees are strongly encouraged to deposit large-scale, human genetic data in the database for Genotype and Phenotype "dbGaP" (https://www.ncbi.nlm.nih.gov/gap). For other data and biospecimens from human genetic or non-genetic studies, awardees are encouraged to use the NICHD Data and Specimen Hub "DASH" (https://dash.nichd.nih.gov/) or other equivalent broad-sharing data and/or biospecimen repositories.

The following resource describing Common Data Elements may be helpful during the planning phases of a project when considering ways to optimize data collection in order to facilitate broad data sharing: https://www.nlm.nih.gov/cde/.

Appendix:

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

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) 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 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.

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 and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

Only the review criteria described below will be considered in the review process. 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 announcement, note the following:

The R61/R33 phased innovation grant supports the investigation of novel scientific ideas or new interventions, model systems, tools or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. An R61/R33 grant application need not have preliminary data, extensive background material or preliminary information; however, such information may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Accordingly, reviewers will focus their evaluation on conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will assign a single impact score for the entire application, which includes both the R61 and R33 phases.

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? For multi-purpose prevention projects, what are the expected benefits of anti-infective strategy and proposed delivery method on public health?

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? For projects that are in or have completed the chemical optimization phase, does the application describe potential routes of delivery/administration?

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.

Transition Milestones

Are the proposed Transition Milestones well defined with quantifiable measures that are appropriate for assessing the success of the R61 phase of the awards? Is it clear how the R33 phase of the study will develop and expand once the R61 Transition Milestones are achieved? If the project requires validation, is the validation plan sufficient to address validation? Do the Gantt charts appropriately reflect the milestones? Are appropriate go/no-go criteria integrated into the milestone criteria?

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.

Not applicable

Not applicable

Not applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and must 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 NICHD, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Child Health and Human Development Council (NACHHD). 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.
• Relevance of the proposed project to the achievement of a balanced product development portfolio, including contraceptive products and medical devices.

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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.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 https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/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 https://www.hhs.gov/ocr/about-us/contact-us/index.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 RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons 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

Daniel S. Johnston, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-827-4663
Email: [email protected]

Sherry Dupere, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-451-3415
Email: [email protected]

Hazel Tignor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-827-5437
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.