Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Allergy and Infectious Diseases (NIAID)
Funding Opportunity Title	Prevention Innovation Program (PIP) (R01)
Activity Code	R01 Research Project Grant
Announcement Type	Reissue of RFA-AI-13-008
Related Notices	March 29, 2016 - This RFA has been reissued as RFA-AI-16-025. June 4, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same.
Funding Opportunity Announcement (FOA) Number	RFA-AI-13-059
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 Prevention Innovation Program (PIP), 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 to establish and maintain a sustainable pipeline for the prevention of HIV acquisition/transmission. The PIP will support discovery and development of novel and under-explored nBP candidates/strategies, nBP delivery strategies, studies of the impact of nBP prevention strategies on genital and gastrointestinal (GI) mucosa function and emerging technologies that support microbicides, pre-exposure prophylaxis (PrEP), and Multipurpose Prevention Technologies (MPT) for prevention of HIV acquisition/transmission.

Posted Date	February 20, 2014
Open Date (Earliest Submission Date)	June 10, 2014
Letter of Intent Due Date(s)	June 10, 2014
Application Due Date(s)	July 10, 2014, 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)	July 10, 2014, 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.
Scientific Merit Review	November 2014
Advisory Council Review	January 2015
Earliest Start Date	April 2015
Expiration Date	July 11, 2014
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). Non-vaccine Biomedical Prevention strategies are composed of, but not limited to, topical microbicides and topical and/or systemic pre-exposure prophylaxis (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, transdermal, injection or by other means) to men and/or women can result in inhibition of the transmission/acquisition of HIV.

• MPT will be defined in this FOA as a combination of a HIV inhibitor(s) with an inhibitor of a Sexually Transmitted Infection (STI) or a licensed contraceptive method. STI inhibitory strategies eligible for support under this FOA as part of a proposed MPT must be clinically and/or epidemiologically associated/linked with increased susceptibility to HIV infection.

The dosing regimen(s) used to deliver the prevention product play a critical factor in the success of the prevention strategy. Evidence is accumulating that daily or coital-associated dosing may not be the optimal way to deliver prevention strategies to some at-risk populations. Analysis of self-reported adherence and plasma drug concentration from the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial where daily dosing in women of 1% Tenofovir vaginal gel or oral Tenofovir or Truvada strongly suggests that adherence was the primary driver for lack of efficacy in this trial. Thus, in an attempt to create new dosing schedules and regimens that may help individuals maintain adherence, this FOA will focus on supporting the development of pericoital and sustained release drug delivery systems (DDS).

For the purposes of this FOA the following pericoital and sustained release definitions will be used:

• Pericoital delivery/ release will be defined as an nBP agent or DDS that will provide a window of at least one (1) week (7 days) of protection against HIV transmission/acquisition after application. Dosing can occur any time during this interval with respect to coitus.
• Sustained delivery/ release will be defined as delivery of an nBP agent that will prevent HIV transmission/acquisition for a minimum of one (1) month after application. Product dosing may be independent of coitus and achieved using single (e.g. injection) or continuous dosing (e.g. intravaginal ring). Achievement of a 30 day protection window using a multiple dosing regimen is not considered sustained release.

Therefore, as a part of the forward looking aspect of research supported under this FOA and its focus on building and maintaining a sustainable pipeline of prevention strategies and delivery systems, the development of products and DDS that provide for longer intervals of protection is encouraged. Development of vaginal products with windows of protection less than one (1) week will be considered non-responsive and will not be reviewed.

Discovery, development and testing of new and innovative nBP candidates, mucosal and HIV inhibition targets and supporting technologies are complex processes that require multi-disciplinary resources and expertise. The PIP program is designed to assist in this effort by supporting the advancement of high-risk and innovative approaches that can substantially advance nBP in six general areas.

• Discovery and exploration of new and novel pericoital and sustained release microbicide and PrEP strategies (singly or in combination) directed against HIV and STIs linked by clinical and epidemiological evidence to enhanced HIV acquisition/transmission.
• Development of novel and innovative pericoital and sustained-release DDS.
• Support of emerging technologies such as engineering and soft/hardware solutions to develop more efficient methods of assessing nBP strategy safety, efficacy, acceptability, and adherence.
• Support for the development of innovative models to address genital and GI mucosa function and integrity that might alter the impact of a prevention strategy, i.e. models of sexual trauma, role of the inflammatory and innate and adaptive immune processes in HIV susceptibility and prevention.
• Development of accurate and reproducible novel and innovative biomedical, electronic, and/or analytical technologies to quantify adherence to products used in clinical trials, placebos and/or verify adherence to a prevention strategy.
• Support pharmacokinetic (PK) and pharmacodynamic (PD) modeling of nBP candidates and strategies in animal models with the objective of creating linkages between tissue and cell concentrations and in vivo observed safety and efficacy.

Given the high-innovation and high-risk research targeted by the PIP program, applicants are required to identify within the application a SINGLE Go/No-Go criterion to be achieved as a deliverable for the Year 2 progress report in order to enable 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.

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 categories. The first category includes 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 may include sexual trauma, age, hormonal and immune status. The second category is the use of animal models for screening/testing of candidates to support their plausibility as clinical candidates. For this latter case the NIAID/DAIDS prevention program strongly encourages and makes the following recommendations when animal model efficacy results are proposed as a mechanism to prioritize nBP development.

• Superiority assessments of the drug product(s) being tested should be used and include appropriate positive control and placebo arms.
• Sufficient numbers of animals should be included in all groups to allow for endpoint statistical analysis. Applicants are cautioned that underpowered studies can reduce reviewer enthusiasm for the application.
• Wherever possible, formulated products characterized for active pharmaceutical ingredients (API) stability and release should be used. The use of unformulated products and vehicle admixtures without establishing some level of drug stability and release is strongly discouraged.
• Where appropriate, the inclusion of secondary endpoints to support the proposed prioritization such as PK, PD and safety measurements (colposcopy, histology, vaginal pH, microbiome analysis and/or the immune response, etc.) is encouraged.

The PIP FOA will not support Phase 1, 2 or 3 clinical trials; however it can support limited clinical research that meets the following criteria. Proposed clinical research must be low risk to participants with limited human exposure to test products. For the purposes of this FOA, Low Risk is defined to be the use of clinical sample collection procedures, i.e. biopsy, Cytobrush, swabbing, or the use of test products with established and documented safety risks. To meet the latter part of this definition, the only allowable test products are: (1) A licensed product, i.e. licensed contraceptive, used only for its approved use or (2) A low-risk placebo. An antiretroviral licensed only for treatment and proposed for use for HIV prevention does not meet this definition. A low-risk placebo is defined as a clinical trial quality product with phase 2B or 3 safety data demonstrating minimal or no impact on the integrity or inflammatory state of the genital and/or GI mucosa, or a Good Manufacturing Practices (GMP) manufactured product that was evaluated in a Good Laboratory Practices (GLP) Rabbit Vaginal Irritation (RVI) studies and showed Draize scale irritation scores lower than Gynol II or other relevant N-9-based control and passed relevant United States Pharmacopeia (USP) microbial limits testing.

Limited clinical research testing designed to address a nBP attribute should incorporate exploratory endpoints such as expression of innate and adaptive immune responses, acceptability or PK studies, and be limited to no more than 20 total participants per proposed study. Studies involving behavioral/social research are limited to no more than 50 participants per proposed study. Studies that exceed these criteria may be categorized as phase 1 clinical trials and will not be reviewed. Applicants may propose multiple studies per application, but are cautioned that poorly justified or duplicative studies could reduce reviewer enthusiasm for the application. Study cohorts may include HIV-positive, specific at-risk populations, such as adolescents, post-menopausal women, specific ethnicities, intravenous drug users (IDUs) and alcohol users and abusers when scientifically appropriate.

Examples of the types of studies that are considered responsive to this FOA include, but are not limited to:

• Development and validation of new pericoital or sustained release nBP candidates. Applicants are encouraged, if applicable, to use chemical, physical, and in silico tools, i.e. computational absorbance distribution, absorption, distribution, metabolism, excretion (ADME), to assist in nBP design, and to use the FDA (U.S. Food and Drug Administration) guidance for preclinical development of antiviral products and the draft guidance for vaginal microbicide development as guidelines for inclusion of relevant antiviral assessments.
• Development of rectal microbicides products or DDS for coital associated or dis-associated use.
• Development of accurate and reproducible biomedical, electronic, and/or analytical technologies that is independent of subject reporting biases to quantify adherence to drug product and/or placebo, when used either remotely by trial participants or during clinical study visits.
• Discovery and/or development of novel pericoital and sustained release DDS. Applicants are encouraged to conduct appropriate in vitro or in vivo animal PK, PD and toxicokinetic (TK) determinations to support the scientific rationale for the chosen nBP delivery route/device.
• Nanotechnology approaches to solve specific problems related to nBP candidate pericoital and sustained delivery, deployment, safety, efficacy and adherence.
• Engineering adaptations (instrumentation, software, hardware, etc.) focusing on creative solutions to minimize sample volumes to quantitatively and/or dynamically analyze tissue and immune responses to nBP candidates and strategies.
• nBP strategies that mediate prevention through the induction or modification of specific adaptive and/or innate immune responses or inflammatory processes and responses to HIV virus. Of interest are specific hypothesis-driven studies into genital and GI tract mucosal immune function and repair, including immune cell trafficking, characterization of tissue-specific immune cells or regulatory cells and their effector function, the role of Toll-Like Receptors (TLRs) and inflammasome(s) in HIV infection/prevention, and how the microbiome may alter genital and GI mucosa integrity and susceptibility to HIV infection. Following the prevention of infection with an nBP strategy, the fate of tissue-associated virus and its effect on the immune response and tissue integrity are also of interest. The role of the duration of the nBP pericoital and sustained release exposure (acute, chronic, and episodic) in modulation of these factors is an additional interest.
• Development of combination nBP strategies. This may include combinations of individual candidates 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.
• Development of new MPT strategies using combinations of anti-HIV retrovirals and hormones. If the non-contraceptive component is an anti-STI drug, then it must meet the definition for MPT composed of STIs given above. Copper or hormone releasing intrauterine devices (IUDs) as the contraceptive component of an MPT are responsive.
• A genetically modified organism(s) (GMO) used as a DDS to deliver two (2) or more specific inhibitors of HIV (combination inhibitor) is responsive. Both inhibitors must have the potential to inhibit HIV transmission /acquisition and be co-expressed from the GMO.
• 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 preferred biophysical properties of an nBP product or strategy. In this latter case it is essential for the applicant to demonstrate the relevance and need for the studies to support the development of 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. Clinical research that uses clinical specimens or involves collection of behavioral or social data or uses allowable test products may be supported under this FOA as defined above.
• Applications proposing development of a vaginal coital (as defined above) PrEP, Microbicide or MPT product or DDS. However, development of rectal coital products or DDS is responsive.
• Activities that are intended solely for enabling/facilitating clinical studies to be conducted with non-PIP funds. This includes activities that support the administrative preparation/submission of a an Investigational New Drug (IND), Investigational Device Evaluation (IDE) and/or New Device Exception (NDE) application to the FDA or other regulatory bodies, or to produce clinical supplies for future trials. This does 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, e.g. models of sexual trauma, genital or GI tract inflammation.
• Generalized or wholly descriptive studies which use exogenous or endogenous hormone exposure in cell lines, animals, or humans to assess changes which might be a potential factor in HIV susceptibility. Applications focused on mechanistic interactions of endogenous and exogenous hormones with the genital and GI mucosa and their impact on epithelial integrity, receptor usage, signaling and cross-talk, and interaction with the immune system to define cellular and genital and GI tissue responses to exogenous and endogenous hormones are responsive.
• Random or bulk screening of chemical or natural product libraries or collections to discover nBP candidates, including development of an uncharacterized natural product consisting of a complex mixture of potentially active and inactive ingredients.
• Development of non-specific agents/products/drugs/candidates as nBP. Non-specific agents for the purposes of this FOA are defined as agents that display broad anti-microbial activity, in the absence of pathogen specificity (nonspecific killing of viruses, parasites, yeast, and pathogenic and beneficial bacteria). A specific agent for the purposes of this FOA is any agent that has a defined mechanism of action, non-toxic to beneficial Lactobacilli spp. and does not induce tissue immune cell infiltration and inflammation. Applicants proposing a "specific agent" nBP having chemical, biophysical and/or antimicrobial properties that may potentially label it as a "non-specific agent" are strongly encouraged to include appropriate preliminary mechanistic safety and/or efficacy data demonstrating its specificity.
• Applications proposing broadly generalized global assessments using genomic, proteomic, scriptomic, and microbiome analysis technologies to identify potential targets or responses to nBP are discouraged. Applications proposing use of these technologies should implement them in a focused manner designed to support an existing model, observation or scientific hypothesis, in contrast to using these methods to find/hunt for possible immune, metabolic or organism interaction pathways to assign to observed phenomena.
• New development or additional development of the DDS or drug product for the following products:
  • Tenofovir (TFV, PMPA, (R)-9-(2-Phosphonoylmethoxypropyl) adenine) or Tenofovir Disoproxil Fumarate (TDF or Viread ) as a single microbicide or for topical or systemic delivery as a PrEP strategy for coital, pericoital, or sustained release is not responsive to this FOA and will be not be reviewed. TFV or TDF may be a component of an nBP combination strategy, if the proposed combination is not already in phase 1 clinical testing. TFV or TDF single products may be used as controls or probes to show equivalence to existing delivery approaches using PK and PD endpoints.
  • Development of new hormonal or non-hormonal contraceptive or spermicidal products. All proposed nBP research (MPT development) that includes contraceptive products must use licensed products,
  • Over-the-counter products (OTC) or non-specific vaginal and/or female/male rectal health products, including lubricants, to prevent HIV transmission,
  • 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, and
  • N-9 (Nonoxynol-9).
• Applications proposing nBP strategies or candidate development without antiviral activity to HIV.
• Development of microbicides for environment decontamination or control.
• Development of microbicides or PrEP for treatment of STIs and bacterial infections associated with oral, pulmonary or iatrogenic infection or control.
• MPT strategies which use a barrier device as a primary mode for HIV prevention. Use of condoms (male or female), as the HIV prevention component in an MPT, 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 and it meets the criteria for pericoital or sustained release DDS, as described above.
• Studies proposing the development or optimization of a Genetically Modified Organism (GMO) as a DDS for delivery of a single nBP candidate or use of bacteria selected or engineered for specific characteristics designed to create a "hostile microenvironment" to HIV and/or STIs.
• Applications proposing any form of vaccine development (new mucosal vaccine, vector, insert, or delivery system), or use of vaccines as an immunomodulatory element of a combination microbicide, PrEP or MPT prevention strategy. This does not preclude the use of gene-vectors to deliver an nBP product for constitutive expression of the nBP in the genital or GI mucosa.
• Basic behavioral research designed to develop broadly usable measures of nBP use, or generalized interventions to reduce HIV incidence. Including surveys and studies to provide information on community/ individual attitudes/acceptability toward hypothetical or theoretical nBPs or education to support introduction of an nBP. Included are structural and/or behavioral interventions to enhance projected product use or prepare for product roll-out or introduction.
• Development of methods to quantify adherence that depend on the use of radioisotopes or unassisted visual assessments of a dye stained applicator. Applications proposing detection of mucosal secretions on applicators using a staining approach must incorporate a quantifiable analytical endpoint.

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 intends to commit $2.4 million in FY 2015 to fund 4 - 6 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 single Go/ No-Go decision criterion 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. 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.

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.
National Institute of Allergy and Infectious Diseases (NIAID)
6700 B Rockledge Drive, Room 3133
Bethesda, MD 20817 (use zip 20892 for courier)
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.

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

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

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

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

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

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

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

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

Research Strategy: Applicants must provide a section with a single, clearly identified Go/No-Go decision criterion for year 2 of the application. Applicants are required to identify in the application a single Go/No-Go decision criterion 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 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.

The Go/No-Go criterion chosen by the applicant must identify a critical parameter that is essential for the success of the proposed research in subsequent years. The Go/No-Go criterion should be specific to the proposed research and represent a quantifiable outcome. A restatement of an application specific aim is not considered an adequate Go/No-Go criterion, and lack of a sufficiently robust Go/No-Go criterion may reduce enthusiasm of the peer review panel for the proposed research.

Selected examples of possible Go/No-Go criterion 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 an applicant chosen, single specific criterion that is essential for the success of the proposed research in subsequent years.

If the application includes a Targeted Product Profile (TPP) to be used to support the development and validation of candidates, the TPP may be placed as a table in the Research Strategy Section. Applicants are encouraged to capture properties in table format that lists the product attributes and both the optimal and minimally acceptable chemical and physical properties of the candidate or DDS. Examples of potential product attributes that can be captured are: product release profile of the DDS, delivery/injection/implant volume, pharmacokinetic (PK) maximums and minimums, stability and storage requirements, desirable physical attributes, acceptability, cold chain requirements and feasibility of GMP production. Applicants are advised that the proposed TPP should be used as a tool for identifying the optimal candidate/DDS proposed in this application, and therefore is less complicated and comprehensive than the FDA required TPP used to map and guide regulatory responses for the complete product development pathway from nonclinical studies to licensure.

If the research strategy includes clinical research, applicants should include a discussion as to how this research meets the FOA-defined criteria for low risk.

The proposed research may require reliance upon relational and/or inferential data to establish the potential for research impact/success rather than substantial experimental data directly supporting application objectives.

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.

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

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

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

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.

See more tips for avoiding common errors.

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-13-030.

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 high-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 substantial 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?

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 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? Does the approach meet the FOA-defined criteria for low risk clinical research? For the purposes of this FOA, Low Risk is defined to be the use of clinical sample collection procedures, i.e. biopsy, Cytobrush, swabbing, or the use of test products with established and documented safety risks. See Section 1, Clinical Research for more information on low risk clinical research.

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?

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 Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children

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.

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 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.

Year 2 Go/ No-Go Decision Point

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.

Year 2 Go/No-Go Criterion

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

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Finding Help Online: http://grants.nih.gov/support/index.html

TTY: 301-451-5939
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 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]

Kristen Porter, Ph.D
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-292-4783
Email: [email protected]

Peter R. Jackson, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-496-8426
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.