Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Allergy and Infectious Diseases (NIAID)
Funding Opportunity Title	Preclinical Innovation Program (PIP) (R01)
Activity Code	R01 Research Project Grant
Announcement Type	New
Related Notices	March 29, 2016 - This RFA has been reissued as RFA-AI-16-025. February 20, 2014 - This RFA has been reissued as RFA-AI-13-059. August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications.
Funding Opportunity Announcement (FOA) Number	RFA-AI-13-008
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.855, 93.856
Funding Opportunity Purpose	This Funding Opportunity Announcement (FOA), the Preclinical Innovation Program (PIP), issued by NIAID, encourages Research Project Grant (R01) applications in non-vaccine biomedical prevention (nBP) research. The PIP is intended to support high risk/innovative research and development efforts designed to establish and maintain a sustainable pipeline of nBP candidates, drug delivery systems (DDS) and supporting technologies for the prevention of HIV acquisition/transmission. The PIP will support novel and under-explored approaches to strengthen and maintain an innovative pipeline of nBP strategies including microbicides, pre-exposure prophylaxis (PrEP), and Multipurpose Prevention Technologies (MPT). To accomplish this, the PIP will also support a range of nBP DDS including, but not limited to, pericoital and sustained delivery of single and combination candidates and strategies using gels, films, intravaginal rings (IVR), oral, implant and/or injection delivery methods. The PIP is a replacement program for the Microbicide Innovation Program (http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-10-011.html) and investigators are urged to read the current FOA closely to identify critical differences between this and previous programs.

Posted Date	March 7, 2013
Open Date (Earliest Submission Date)	July 1, 2013
Letter of Intent Due Date(s)	July 1, 2013
Application Due Date(s)	August 1, 2013, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	August 1, 2013, by 5 PM local time of the applicant organization.
Scientific Merit Review	December, 2013
Advisory Council Review	January, 2014
Earliest Start Date	April, 2014
Expiration Date	August 2, 2013
Due Dates for E.O. 12372	Not Applicable

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 purpose of the Preclinical Innovation Program (PIP) is to support novel, high-risk and under-explored strategies in the field of non-vaccine Biomedical Prevention (nBP). A safe, effective, acceptable nBP strategy that prevents the sexual transmission of HIV could play a major role in world-wide reduction of the over 7,000 new HIV infections per day, potentially saving millions of lives. nBP strategies are composed of, but not limited to, topical microbicides and topical and/or systemic PrEP, and Multipurpose Prevention Technologies (MPT). All of these strategies when applied topically to genital and gastrointestinal (GI) tract mucosa or delivered systemically (oral, implanted and injected) to men and/or women can result in inhibition of the transmission of HIV and/or other sexually transmitted infections (STI) that may act as susceptibility co-factors for HIV transmission and acquisition. MPTs strategies may be composed of combinations of HIV and STI inhibitory strategies, including the prevention of conception using licensed contraceptive methods. The term nBP will be used to collectively identify microbicide, PrEP, and MPT prevention strategies for the purpose of this FOA.

The discovery, development and testing of nBP candidates, targets and supporting technologies are complex processes that require multi-disciplinary resources and expertise to support the discovery/identification and development of candidates that are safe, effective, and acceptable. The PIP program is designed to assist in this effort by supporting the advancement of novel scientific ideas, models, tools, agents, targets, technologies and strategies that can be implemented iteratively to substantially advance nBP in six general areas.

(1) Discovery and exploration of new and novel microbicides and PrEP strategies (singly or in combination) directed against HIV and sexually transmitted infections (STIs) linked by clinical evidence to enhanced HIV acquisition/transmission.

(2) Development of sustained-release formulations using DDS such as intravaginal rings (IVRs), injection and implants to disassociate coitus from prevention candidate application. Oral delivery methods may also be used to achieve coital-disassociation.

(3) Support emerging technologies or models that contribute to the development of new and/or more efficient methods of assessing nBP strategy safety, efficacy, acceptability, and adherence.

(4) Support the development of quantitative biomedical methods to measure adherence to nBP strategies.

(5) Support pharmacokinetic (PK) and pharmacodynamic (PD) modeling of nBP candidates and strategies in animal models to create linkages between tissue and cell concentrations and in vivo observed safety and efficacy.

(6) Support the development of new technologies, approaches and processes, including engineering and soft/hardware solutions, to support the nBP pipeline.

Given the high-innovation and -risk research targeted by the PIP program, applicants are required to identify in the application a single Go/ No-Go decision point to be achieved as a deliverable for the Year 2 progress report and for advancement to years 3 -4 funding. The Go/ No-Go criterion will be referenced in the notice of award. Achievement of the stated goal (Go) will enable a total of 4 years of support, while failure to achieve the stated goal (No-Go) will result in negotiation of a reduced budget for year 3 and award close out. The Go/ No-Go criterion chosen by the applicant should identify a critical parameter that is essential for the success of the proposed research in subsequent years. The provided Go/No-Go criterion should be specific to the proposed research and represent a quantifiable outcome of the research. Restatement of a specific aim is not considered to be an adequate Go/ No-Go criterion, and lack of a sufficiently robust Go/ No-Go criterion may reflect poorly on the overall enthusiasm of the peer review panel for the proposed research. Selected examples of possible Go/No-Go criteria are:

• The identified lead candidate will have (Fill in blank) potency or have the following specific (Fill in blank) characteristics.
• The formulated candidate will demonstrate (Fill in blank) potency and/or (Fill in blank) specific safety outcomes in animal model(s).
• The candidate, formulation and/or device will achieve a target tissue concentration of (Fill in blank).
• The proposed DDS and/or formulated candidate will deliver/release drug for (Fill in blank) hours/ days/ weeks /months and at (Fill in blank) concentration, or
• The technology proposed will measure (Fill in blank) under the following conditions (Fill in blank) with (Fill in blank) precision.

In these examples "Fill in Blank" denotes the applicant specified critical parameter that is essential for the success of the proposed research in subsequent years

Applicants may include research that uses animal models such as humanized mice and/or nonhuman primates (NHP) for safety and/or efficacy determinations of the nBP strategies or candidates. For the purposes of this FOA, animal studies are divided into two types. The first are studies that address the basic and developmental science issues of virus transmission within the context of the nBP candidate or strategy. Examples are assessments of environmental and physiological factors resulting from nBP exposure that might alter susceptibility, acquisition and dissemination of virus at the mucosal tissues. These include the endogenous hormonal state, use of exogenous hormones, pregnancy, age and immune status. The second category is the use of animal models for screening/testing candidates to support their plausibility as clinical candidates. For this latter case, the recent trends of (1) investigator use of animal studies as gateways for clinical selection and establishment of biological plausibility in the absence of a requirement for demonstration of animal model efficacy by the FDA, (2) the cost of using these resources as screening tools , (3) limited availability of some species of animals and (4) the cost of producing and maintaining some animal species/subspecies/models for relevant experimental periods has led the NIAID/DAIDS prevention program to make specific recommendations regarding these types of studies. The NIAID/DAIDS prevention program strongly encourages investigators proposing the use of animal models as gateways to design robust experiments for assessing efficacy and safety of nBP. Robust experiments are defined as studies that: (1) include superiority assessments (selecting best candidate or more potent candidate) with positive control and/or placebo arms, (2) use of a sufficient number of animals in all groups to allow for endpoint statistical analysis, and (3) studies that use a formulated product. Studies should be designed to allow a statistical assessment of the outcomes. Applicants are cautioned that inclusion of too few animals in groups can reduce enthusiasm of the study section for the application. Selection of animal numbers should be supported by power calculations, and for NHP studies applicants should consider group sizes of 6 or more animals. The formulated product used for testing should have undergone sufficient development to establish product stability, retention of antiviral activity and release from the dosing vehicle. Studies in which unformulated prevention candidates are mixed in vehicles without establishing some level of stability or release from the vehicle are strongly discouraged in this FOA. The proposed animal studies, wherever possible, are encouraged to include additional study endpoints such as PK and PD determinations and safety measurements (colposcopy, histology, monitoring of vaginal pH, microflora analysis and/or measurement of adaptive/innate immune markers, etc.). Applicants performing PK and PD studies in these models are encouraged to incorporate adequate pharmacological and analytical expertise to select optimal sampling regimes and perform analysis of outcomes.

Examples of the types of studies that are considered responsive to this FOA and could be supported under this program include, but are not limited to:

• Development and validation of new nBP candidates that interact with specific steps in the viral replication cycle and/or with cellular pathways that prevent HIV transmission and acquisition. Applications proposing screening efforts must direct their efforts to a specific anti-HIV or cellular target that has relevance to HIV prevention. The selection of the optimal candidate should be defined using a Targeted Product Profile (TPP). If screening algorithms are used to identify the best lead candidate or prevention strategy, then the algorithm should provide clear and quantifiable Go/ No-Go decision points for identifying superiority. Selection and optimization of the candidate should be performed in an iterative manner to achieve a TPP or algorithm-defined outcome. Applicants are encouraged to incorporate the chemical, physical and in silico tools of medicinal chemistry and rational drug design in their applications. All applications proposing identification of new candidates must, in addition to providing a quantifiable selection algorithm or TPP, address critical antiviral properties such as mechanism of action range of antiviral action, toxicity on multiple cell types, lack of toxicity to Lactobacilli sp., effect of relevant body fluids (cervicovaginal fluid, semen, etc.) on antiviral activity and toxicity, and the potential to engender viral resistance. Applicants are encouraged to use the FDA (U.S. Food and Drug Administration) guidance for preclinical development of antiviral products (http://www.fda.gov/OHRMS/DOCKETS/98fr/05d-0183-gdl0002-01.pdf) as a guideline for designing quantitative algorithms, TPPs and creating Go/No-Go decision points.
• Applications may propose discovery and/or development of oral, injection or implantable DDS and strategies. Applicants are encouraged to include plans to conduct appropriate PK, PD and toxicokinetic (TK) determinations to support the rationale for the chosen delivery route/device. Applicants are encouraged to develop target values for TK, PK and/or PD and incorporate them into TPPs to describe the DDS and the application required Go/ No-Go decision point. Development may include optimization of existing DDS to create a significant improvement over existing pericoital and coitally-independent sustained delivery devices/approaches. Applicants are encouraged to demonstrate superiority and feasibility through the appropriate in vitro and in vivo safety and efficacy assessments.
• The use of nanotechnology approaches to solve specific problems related to nBP candidate sustained delivery, deployment, safety and efficacy.
• Development, adaption and engineering of hardware and/or software solutions that will afford for novel approaches to analyzing the cellular, tissue and systemic effects of nBP. Engineering adaptations can encompass a wide range of development processes focusing on creating solutions to quantitatively and dynamically analyze responses to nBP candidates and strategies using live or dead cells and tissues.
• nBP strategies that mediate prevention through the induction or modification of adaptive and/or innate immune responses or inflammatory processes contributing to HIV acquisition/transmission in the male and/or female genital and/or GI tract to prevent transmission. If a vaccination strategy is used to modify immunity, the primary mode of prevention studied in the application must be the nBP strategy and not the development of a new mucosal vaccine, vector, insert, or delivery system. The vaccine should have established correlates of protection and demonstrable efficacy in an animal model. Studies proposing any form of vaccine development other than optimization/dosing of the vaccine/nBP combination are non-responsive and will be returned without review.
• Assessment of the effect of nBP candidates and strategies on the male and/or female genital and/or GI tract innate and adaptive immune responses and/or induction of inflammation as correlates of product safety, efficacy and acceptability. This may include applications designed to identify and validate a defined panel of surrogate safety and/or efficacy biomarkers using genomic and/or proteomic approaches. This may also include efforts to understand the dynamics (trafficking, activation status) of susceptible cells in target tissues and their effect on nBP safety and efficacy. Also of interest is the role of the duration of nBP exposure (acute, chronic, and episodic) on modulation of biomarkers and efficacy endpoints. It is expected that applications would validate proposed markers against a range of nBP candidates.
• Development of combination nBP strategies using combinations of candidates belonging to a specific nBP category or combining nBP types into a prevention package. Proposed combination strategies that include activity against an STI linked to HIV susceptibility/transmission/acquisition must demonstrate and maintain antiviral activity and efficacy against HIV. Combination strategies may integrate multiple forms of nBP prevention as part of the development of an overall strategy/approach, but in all cases the focus of the application must be development/optimizing the effectiveness of the component that prevents HIV infection. Combination nBP strategy development may include the development of MPT strategies, which incorporate contraception. If the proposed MPT strategy contains a contraceptive, it must be a licensed contraceptive product, such as a hormone-based contraception product.
• Assessments of baseline behavioral and social parameters that could directly affect nBP adherence or acceptability. This may include development of specific tools or measures designed to identify acceptability of formulated nBP or delivery strategies. It may also include preliminary assessments of baseline conditions or practices within specific nBP target populations that could directly inform on required biophysical properties of a nBP product or strategy. In this latter case it is essential for the applicant to demonstrate the relevance and need for the studies to the proposed nBP.

Applications proposing research in the following areas will NOT be considered responsive to this FOA and will not be reviewed:

• Applications proposing Phase I, II or III clinical trials or first in-human studies will not be supported and will not be reviewed. Clinical research that uses clinical specimens or involves collection of behavioral or social data may be supported under this FOA. Applicants are strongly urged to discuss any application containing clinical research elements with Program staff prior to submission.
• Since this FOA does not support clinical trials, activities included in the R01 that are intended solely for enabling/facilitating clinical studies to be conducted with non-PIP funds are not responsive and will not be reviewed. Examples are specific aims, objectives, Go/No-Go decision points and/or milestones that: (1) are intended solely to support the administrative preparation/submission of a pre-IND, IND and/or IDE to the FDA or other regulatory body, (2) propose meetings with the FDA or other regulatory bodies, and/or (3) describe production of clinical supplies for future trials. These nonresponsive criteria do not preclude research aimed at optimizing specific nBP production processes, such as developing unique and innovative methods to produce a candidate, formulation and/or DDS. Nor do they preclude incorporating research or testing that could contribute to and/or be included in a future IND submission, such as preclinical virology or animal testing.
• Development of new animal models of HIV or STI infection. Improvement of existing in vivo safety and efficacy models are responsive, if the improvements are validated in the context of the development of a nBP candidate(s) or strategy.
• Development of non-specific agents as single or combination nBP. Non-specific agents for the purposes of this FOA are defined as agents that display broad anti-microbial activity in the absence of organism specificity. Examples are detergent, surfactant or non-specific membrane-active agents such as reactive oxygen and/or oxidizing/reducing agents. These candidates are often characterized by broad nonspecific killing of viruses, parasites, yeast and bacteria, including beneficial Lactobacilli sp. Applicants proposing a nBP candidate having chemical/biophysical properties and/or a broad range of antimicrobial activity that may be identified by the peer review panel as potentially belonging to the class of non-specific agents are strongly encouraged to include appropriate preliminary mechanistic data as well as safety and efficacy data to justify development of such a candidate as a specific agent . A specific agent for the purposes of this FOA is any agent that has a defined or definable mechanism of action and/or is non-toxic to beneficial Lactobacilli sp. and when applied to genital mucosa is non-disruptive/toxic and does not induce tissue infiltration and inflammation. Applicants are cautioned that product/candidate safety data from mucosal tissues (skin, oral, etc.) other than the female or male reproductive and GI tract do not necessarily equate to safety in these compartments. Likewise, human exposure and experience with products or formulary components such as vaginal and/or rectal medicants, or for health purposes, do not necessarily equate to safety for use as an nBP or nBP constituent.
• New development or additional development of the following products:
  • N-9 (Nonoxynol-9),
  • Development of new hormonal or non-hormonal contraceptive or spermicidal products. All proposed nBP research (MPT development) that includes contraceptive products must use licensed commercial products,
  • Over-the-counter products (OTC) or non-specific vaginal and/or female/male rectal health products, including lubricants, to prevent HIV transmission,
  • Tenofovir (TFV, PMPA, (R)-9-(2-Phosphonoylmethoxypropyl)adenine) or Tenofovir Disoproxil Fumarate (TDF or Viread ) as a single microbicide for topical or systemic delivery as a PrEP strategy for pericoital or sustained release is not responsive to this FOA and will be returned without review. TFV or TDF may be a component of an nBP combination strategy. TFV or TDF may also be used to show equivalence to existing delivery approaches using PK and PD endpoints. The goal of any application using TDF or TFV cannot be the development of a single nBP or delivery system for either of these molecules, and
  • Development of sulfonated polysaccharides or other large molecular weight charged polyanions as a single prevention product. Strategies using these entities in combination with other nBP candidates will be considered responsive to this FOA.
• Applications proposing nBP strategies or candidate development without antiviral activity to HIV, or that show activity to STIs with no concomitant activity to HIV, or to STIs that do not have clinical evidence of increasing the risk of HIV transmission are not responsive to this FOA. This includes proposed development of anti-microbial or prevention strategies to non-STI pathogens such as bacterial infections associated with oral, pulmonary, skin or surgical conditions. Applications proposing environmental decontamination strategies are not responsive.
• MPT strategies which use a barrier device as a primary mode for HIV prevention are not responsive. Use of condoms (male or female), as a HIV Prevention strategy as part of an MPT strategy, are not responsive. MPT strategies based on adding a gel to a barrier device are not encouraged, unless there is re-engineering to the barrier device to make the incorporation of the nBP candidate more user-friendly, acceptable and/or efficacious.
• Random or bulk screening of chemical or natural product libraries or collections to discover nBP candidates. Before including a significant screening component into an application, applicants are encouraged to discuss its scope and intent with Program to determine responsiveness.
• Development of an uncharacterized natural product as an nBP or MPT strategy consisting of a complex mixture of potentially active and inactive ingredients.
• Studies proposing the development or optimization of genetically modified organisms (GMO) for delivery of a single nBP candidate or use of microflora (selected for specific characteristics or bioengineered) to prevent HIV and/or STI transmission and/or acquisition.
• Applications proposing any form of vaccine development (new mucosal vaccine, vector, insert, or delivery system) are not responsive and will not be reviewed.. Vaccines may only be used in applications to this FOA as described above in the responsive criteria.
• Basic behavioral research designed to develop broadly usable measures of nBP use, or generalized interventions to reduce HIV incidence. This includes community and stakeholder surveys and studies designed to provide local, community or population level assessment of attitudes toward specific products and/or education to support a proposed introduction of a theoretical or actual nBP.

Funding Instrument	Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Application Types Allowed	New The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIAID/DAIDS intends to commit $3,500,000 in FY 2014 for funding 4 to 8 awards.
Award Budget	Application budgets are limited to a direct cost of $400,000 per year.
Award Project Period	Applicants will submit a 4 year R01 application, and are required to identify a Go/ No-Go decision point to be achieved as a deliverable for the Year 2 progress report. Achievement of the stated goal (Go) will enable continuation of the R01 for a total of 4 years, while failure to achieve the stated goal (No-Go) will result in negotiation of a reduced budget for Year 3 and award close out.

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 and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

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, 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 should be sent to:

Peter R. Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases (NIAID)
Room 3133, MSC 7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616 (for Express Mail 20817)
Telephone 301-496-8426
Fax: 301-480-2310
Email: [email protected]

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

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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: All applications must contain a detailed, non-modular budget. Applicants should ignore the following warning that will be generated for applications requesting budgets of $250,000 or less per year: The direct cost requests of $250K or less each year (on the 424 R&R Budget page section F-K) must be in modules of $25K, using the PHS 398 Modular Budget Form and not the R&R Budget Form. Incorrect applications may be delayed in the peer review process or rejected."

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:

Research Strategy: Applicants must provide a section with a clearly identified Go/ No-Go decision point for year 2 of the application. Applicants are required to identify in the application a single Go/ No-Go decision point to be achieved as a deliverable for the Year 2 progress report and for advancement to years 3 -4 funding. The Go/ No-Go criterion will be referenced in the notice of award. Achievement of the stated goal (Go) will enable a total of 4 years of support, while failure to achieve the stated goal (No-Go) will result in negotiation of a reduced budget for year 3 and award close out. The section may be placed at the end of the Research Strategy Section, and applicants should consider the use of timelines and Gantt charts to support the choice and timing of the Go/ No-Go decision.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) 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.

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.

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.

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.

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Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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 R01-based PIP program is intended to identify high-risk and innovative research that can contribute significantly to the preclinical nBP prevention pipeline. Accordingly, evaluation of the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge and understanding of nBP-mediated prevention will be critical to achieving the goals of this program and submitted applications. Although, preliminary data can play a significant role in providing a justification or rationale for the approach taken and the projected impact of proposed research, the high level of innovation and risk requested for PIP applications may not be supported by extensive preliminary data. Thus, judgments regarding potential success for the proposed research may require reliance upon relational and/or inferential data to establish the potential for research impact/success rather than experimental data directly supporting application objectives.

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.

Significance

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?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?

Innovation

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? Is the application innovation embodied by the advancement to the field of nBP prevention by provision of new candidates, strategies and/or technologies required to sustain and/or maintain a pipeline of nBP prevention strategies and technological infrastructure?

Approach

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 clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

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?

Go/ No-Go Decision Criteria

Given the critical nature of the Go/ No-Go decision criterion for continuation of funding past year 2 of the award, is the proposed Go/No-Go decision criterion well-defined with a quantifiable and measurable outcome appropriate for assessing the success of the first 2 years of the application? Is the Go/No-Go decision criterion sufficiently described to enable a clear decision about its attainment? Given the potential benefits and innovation of the proposed research, is the applicant provided Go/No-Go decision criterion commensurate with the overall projects proposed advancement of the candidate, target, technology or strategy? Does the Go/ No-Go decision reflect the impact of the proposed research on the nBP pipeline and field?

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.

Protections for Human Subjects

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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.

Biohazards

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.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

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 should not consider them in providing an overall impact score.

Applications from Foreign Organizations

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.

Select Agent Research

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).

Resource Sharing Plans

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) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NIAID, 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 Allergy and Infectious Diseases Council. The following will be considered in making funding decisions:

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

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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

Given the high-innovation and -risk research targeted by the PIP program, applicants are required to identify in the application a single Go/ No-Go decision point to be achieved as a deliverable for the Year 2 progress report and for advancement to years 3 -4 funding. The Go/ No-Go criterion will be referenced in the notice of award. Achievement of the stated goal (Go) will enable a total of 4 years of support, while failure to achieve the stated goal (No-Go) will result in negotiation of a reduced budget for year 3 and award close out.

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 annual Non-Competing Progress Report (PHS 2590 or RPPR) 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.

In the Year 2 progress report, awardees must address the status of the project in regards to the single Go/ No-Go decision point identified in the application. Achievement of the stated goal is required for future year funding.

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)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Phone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

Jim A. Turpin, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-451-2732
Email: [email protected]

Peter R. Jackson, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone 301-496-8426
Fax: 301-480-2310
Email: [email protected]

Ann Devine
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-402-5601
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 Parts 74 and 92.