Part 1. Overview Information

Participating Organization(s)
National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Allergy and Infectious Diseases (NIAID)

Funding Opportunity Title
Long-acting Drug Delivery Systems for ART Optimization in HIV-1 Infected Children (R61/R33 Clinical Trial Not Allowed)
Activity Code
R61/R33 Exploratory/Developmental  Phased Award
Announcement Type
New
Related Notices
None
Funding Opportunity Announcement (FOA) Number
RFA-AI-18-057
Companion Funding Opportunity
None
Catalog of Federal Domestic Assistance (CFDA) Number(s)
93.855
Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to accelerate development of safe and effective long-acting drug delivery systems (LA-DDS) for improved, simplified treatment of HIV-1 in children. This FOA invites applicants engaged in the development of existing LA-DDS platforms at early product development stages to perform specific preclinical activities that enable product optimization and accelerated translation to HIV-1 infected children. Collaborative research partnerships with industry are required.

Key Dates

Posted Date

November 20, 2018

Open Date (Earliest Submission Date)
February 13, 2019
Letter of Intent Due Date(s)
February 13, 2019
Application Due Date(s)

 Only accepting applications for the AIDS Application Due Dates listed below.

AIDS Application Due Date(s)
March 13, 2019 by 5:00 PM local time of applicant organization. All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on thisdate.

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
July 2019
Advisory Council Review
October 2019
Earliest Start Date
December 2019
Expiration Date
March 14, 2019
Due Dates for E.O. 12372
Not Applicable
Required Application Instructions
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to accelerate development of safe and effective long-acting drug delivery systems (LA-DDS) for improved, simplified treatment of HIV-1 in children. This FOA invites applicants engaged in the development of existing LA-DDS platforms at early product development stages to perform specific preclinical activities that enable product optimization and accelerated translation to HIV-1 infected children. Collaborative research partnerships with industry are required.
 

Background

Despite significant advances in prevention of maternal-to-child transmission of HIV and antiretroviral (ARV) scale up in HIV-infected children, pediatric HIV still constitutes an important part of the global HIV burden. In 2017 there were approximately 1.8 million prevalent and 180,000 new infections in children less than 15 years old and 2.1 million prevalent infections and 260,000 new infections in children 10-19 years old. The proportion of HIV-infected children receiving antiretroviral treatment (ART) and achieving viral suppression worldwide continues to increase but, in most places, falls short of meeting UNAIDS' 90-90-90 targets. Currently available ART regimens for children have limitations including: suboptimal viral suppression, poor adherence in all pediatric populations but particularly in adolescents, regimen toxicity, and decreased drug penetration at some anatomical sites (lymphoid tissue, central nervous system [CNS]) of HIV replication. In particular, infants and young children experience high rates of pre-treatment drug resistance, hypervariable ARV exposures in early life due to ontogeny of drug metabolizing enzymes (DME) and transporters, lack of appropriate formulations and poor palatability/tolerability of many of the existing formulations. Even in settings where ART is available, other barriers exist contributing to delay of ART administration to young children such as maternal fear of stigma and non-disclosure of HIV status. Pediatric ARV drug development experiences many challenges, and introduction of new ARVs in children lags behind their introduction in adults by years. Generation of preclinical data relevant to inform pediatric studies seldom occurs early in drug development, and product manufacturers are not required to do so. Submission of Pediatric Study Plans (PSP)/Pediatric Investigation Plans (PIP) to regulatory bodies is not required in most cases until the end of Phase II adult studies. Late initiation of development of age-appropriate formulations further delays initiation of studies in young children who are unable to swallow tablets. LA-DDS that can overcome these limitations are needed to significantly simplify dosing requirements and optimize ART outcomes in infants and children, through achievement and maintenance of consistent and effective drug levels in anatomical tissues of high HIV replication. Stimulating critical optimization and preclinical activities at a very early drug development stage could significantly accelerate introduction of promising LA-DDS platforms to pediatric populations across the age spectrum.

Research Objectives and Scope

The objective is to develop a LA-DDS for treating HIV-1 in one or more pediatric age groups. For the purposes of this FOA, the target pediatric age groups are defined as: infants (0-< 2 years), young children (2-< 6 years), older children (6-< 12 years) and adolescents (12-< 18 years). While all pediatric populations are of interest, recent FDA draft guidance encouraging adolescent inclusion in adult studies of antiviral agents, could mean easier transition for these products to adolescents or older children where, limited or no formulation optimization activity may be required, compared to younger children. Therefore, additional emphasis in this FOA is placed in non-adolescent (infants and children) age groups, particularly infants. The proposed LA-DDS may be in preclinical testing or early human clinical testing phase (up to phase 2) in adults but should not have undergone any clinical testing or have imminent plans for such testing in pediatric populations for anti-HIV-1 indications.
 

Responsive applications must include: 

  • A proposed LA-DDS with:
  • Incorporation and simultaneous delivery of a fully active ARV combination
  • Minimum dosing interval of > 4 weeks
  • Applicants who have experience with the proposed LA-DDS, in terms of the development of the LA-DDS for non-pediatric or non-ART applications.
  • An industry partner as defined below.
  • Plans to develop an LA-DDS strategy for one or more pediatric age groups (with particular emphasis on the infants and children age groups as defined above), appropriate for the development stage of the target age group(s) and build/optimize a formulation suitable for chosen age group(s). 
  • An animal antiviral efficacy study of the LA-DDS candidate in the R33 phase in non-human primates (NHP).

Areas of interest include but are not limited to:

  • Sustained/extended release strategies incorporating pharmacokinetic (PK) studies with activities critical to characterizing the DDS sustained/extended release characteristics and capacity such as:
  • Animal PK and pharmacodynamic (PD) studies to support the proposed duration of use and PK parameters.
  • Characterization of the PK tail sufficiently to allow selection of the dosing regimen with such factors as lag, duration and forgiveness interval taken into account.
  • Optimizing to achieve forgiveness intervals of no more than 1/3 of the proposed duration of action of the DDS. Forgiveness interval is defined as the interval in which redosing is recommended to avoid delivering drug below the effective concentration.
  • Studies of PK lag periods (time before establishment of real or predicted effective drug concentrations).
  • Administration strategies such as oral, injection (depot and non-depot forming), implant (non-biodegradable or biodegradable), transdermal (continuous use or short exposure depot-forming), and depot or nondepot forming systems, which may or may not be enabled using nanotechnology and engineering solutions to achieve the required minimal durations of action.
  • Enhanced targeting of anatomical compartments (e.g., secondary lymphoid tissues, gut-associated lymphoid tissue (GALT)), and CNS.
  • Antiviral efficacy and safety of the proposed product(s) within the LA-DDS in animal models.
  • Early assessment of preferred user characteristics in the end user population as defined below is strongly encouraged.

Industry partnership and collaboration. Applications submitted in response to this FOA require substantial collaboration with at least one industrial partner. An industrial partner/collaborator is broadly defined as participation in the application of an individual, group, or unit from a for-profit or not-for-profit pharmaceutical, biotechnology, bioengineering, or chemical company that is large or small, domestic or foreign with an established record in product development. Substantive collaboration is defined as a significant commitment of one or more resources to the project including, but not limited to: research and development plan support/guidance, product development support/guidance, personnel, provision and testing in animal or other laboratory models for evaluation, data management resources and/or regulatory support. Inclusion of a Contract Research Organization (CRO) to provide fee-for-service deliverables without significant participation/scientific collaboration in the research agenda does not meet the definition of an industry partner. Applications from industry are not required to involve collaborators from academic and/or non-profit research organizations, but are encouraged to do so, where appropriate.
 

Preferred user characteristics (PUC) assessment in end user population. Studies using established behavioral and social sciences tools or other assessment approaches to focus on identifying factors that may influence an individual/caregiver's preference for a LA-DDS strategy are strongly encouraged. Such studies must not include clinical trials. Such studies can take place either during the R61 phase or R33 phase.
 

Animal research. Animal studies for LA-DDS optimization in the R61 phase are allowed. Animal models other than NHP can be used for screening/testing LA-DDS candidates to understand overall PK of the antiviral compounds (e.g., PK tail, forgiveness and duration), safety and/or drug-drug interactions (DDI) leading up to the sentinel NHP efficacy study. For the purposes of this FOA, the R33 phase must include an animal antiviral efficacy study in an NHP animal model.
 

Non-responsive Areas of Research

The following activities are non-responsive and will not be reviewed:

  • de novo DDS/small molecule discovery work
  • cGMP manufacture activities
  • Applications proposing development of LA-DDS with durations of action that do not meet the minimum durations defined in the FOA
  • Intravenous infusion of any component of the LA-DDS
  • Use of any live biotherapeutic or vector system (viral, bacterial, fungal, etc.) to produce/deliver the anti-HIV component of the proposed drug product
  • Development of broadly neutralizing antibodies
  • LA-DDS platforms that are in late phases of clinical testing or planned clinical testing in pediatric populations
  • Applications without an industry partner as defined in the FOA

Phased Innovation Awards

This FOA will use milestone-driven, phased research activities with investigator-provided milestones. Support will be provided for up to two (2) years for the R61 phase, and up to three (3) years for the R33 phase, if applicable. Prior to the end of the R61 phase, awardees will submit the R33 transition package, which will be evaluated by NIH Program staff for completion of milestones. R33 transition decisions will be based on successful completion of negotiated transition milestones, Program priorities, and availability of funds. If selected for transition, R61 awards will transition to the R33 award without the need to submit a new application. It is expected that approximately half of the projects funded during the R61 phase will continue into the R33 phase

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

Section II. Award Information

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.

Clinical Trial?
Not Allowed: Only accepting applications that do not propose clinical trials

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards
NIAID intends to commit $3.86M in FY 2020 to fund 3-4 awards
Award Budget

Application budgets are limited to $640,000 in direct costs per year for the R61 award phase and $860,000 in direct costs per year for the R33 award phase.      

Award Project Period

The total project period for an application submitted in response to this FOA is five years. Applicants may request up to two years of support for the R61 phase, and up to three years of support for the R33 phase.      

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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)
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. 
Required Registrations

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.
  • 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.

Eligible Individuals (Program Director/Principal Investigator)
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.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

 

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

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

Page Limitations
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed
Instructions for Application Submission
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.
SF424(R&R) Cover
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Project/Performance Site Locations
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Other Project Information
All instructions in the SF424 (R&R) Application Guide must be followed.
SF424(R&R) Senior/Key Person Profile
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:

In the budget section, applicants should include a budget for planned activities by phase (R61, R33) for the entire five-year award period (up to two years for the R61, up to three years for the R33). 

R&R Subaward Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Cover Page Supplement
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Research Plan
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims: Briefly describe in clearly demarked sections the overall objective(s) and specific aims for both the R61 and R33 phases of the proposed research.

Research Strategy: Describe how the proposed sustained/extended release prototype represents an advancement beyond the products currently being developed, and how the proposed development pathway helps to establish the next generation of products for possible clinical testing in pediatric populations.

Population Targets: Describe clearly the justification for using the pediatric population/age range proposed for prototype development. Applications proposing to use adolescent populations should include additional justification for their choice and inclusion. These can include (but not be limited to) early evidence of increased desirability/acceptability in this population, greater prospects for targeting CNS and/or other anatomical compartments.

LA-DDS Development: Describe the LA-DDS pediatric development plans, including:

  • The antivirals selected and selection process and rationale and how the antiviral will be incorporated into the DDS to achieve the required durations of action.
  • The drug development pathway in terms of the proposed research strategy and how achievement of the proposed R61 and R33 milestones enable product development.
  • The rationale and approach to achieving the duration of action proposed for the sustained/extended release prototype.
  • Suitability of the proposed LA-DDS platform for the target age group(s) in relation to the development stage.
  • Targeted Product Profile (TPP) (optional): applicants may include a TPP to summarize sustained/extended release drug product critical properties and targets for development. Describe the essential product attributes by identifying optimal and minimally acceptable criteria for the drug and its DDS. Product attributes include product release profile and duration of action, optimal dosing regimen, acceptable duration of PK lag periods and tails, maximum and minimum PK targets, PD targets, stability and storage requirements, desirable acceptability/desirability-derived attributes, and cold chain/storage requirements.

Animal Models: For studies using animal models, describe how the animals proposed are appropriate (age and maturity) for the LA-DDS development in the target population; describe the study design features that allow for an assessment of potential safety and effectiveness of the sustained/extended release strategy, including study design elements that support the integrity of the study endpoints. These include descriptions of:

  • The positive control and placebo arms and their role in the study outcome,
  • How the drug products were characterized for stability, drug content and release,
  • How time points and the samples for analysis at these time points were chosen for studies

Preferred User Characteristics (PUC) assessment (strongly encouraged): Describe how PUC will be established and how they are expected to enhance the product development plans. If PUC studies were conducted in a different population, provide evidence that PUC outcomes from other proposed LA-DDS systems in other populations may be used to address PUC for the targeted population(s).

Milestones (required): In a clearly labeled section, provide milestones for BOTH the R61 and R33 phases of the award. Proposed milestones should describe research outcomes by providing quantifiable measures for success within the R61 and R33 phases of the award. Milestones that are a restatement of application Specific Aims do not meet the definition of milestones used here. Descriptions of the milestones must include Go/No-Go statements to support critical parameters of the milestone that will determine whether the research should move forward or cease due to pediatric product development failures.

Milestones should address critical points required for sustained/extended release products. The following milestones are examples that may be included:

  • Demonstration of proposed duration of action.
  • Definition of optimal dosing regimen including PK lag and tail.
  • Identification of active pharmaceutical ingredient (API) and API-DDS DDI.
  • Characterization of anti-HIV efficacy of the sustained/extended release prototype in an animal model.
  • Acceptability/desirability outcomes and integration into sustained /extended release product development for pediatric indication.

Industry Partner: In a clearly labeled section, describe the role of the industry partner as a collaborator, including the activities and processes conducted by the partner. If proposing the use of a CRO, clearly demonstrate how the CRO is making substantive contributions to the proposed research in terms of scientific input, as well as contributions to and involvement in strategic planning and development. Applications from industry should describe the advantages that sole industry sponsorship brings to the application. Industry applicants should describe how an academic collaborator(s), if proposed, will be integrated into the proposed research. If industry is proposing a virtual effort (contracting out all or part of the research), describe the oversight for the contracted elements of the plan.

Letter of Support:  Provide a letter of support indicating the availability of non-human primates for experiments in the R33 phase from a non-human primate facility that includes infant and juvenile animals and/or a breeding program.

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

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information
When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

PHS Assignment Request Form
All instructions in the SF424 (R&R) Application Guide must be followed.
 

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

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Post Submission Materials
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

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

Overall Impact
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).
Scored Review Criteria
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

 

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

 

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

Specific to this FOA

Do the PD(s)/PI(s) or the research team have experience in the development of LA-DDS?

 

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

 

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

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

Specific to this FOA  

Is the LA-DDS strategy appropriate and justified for use in the target population/age group? If adolescence is chosen as the target age group, is the additional justification for this age group appropriate? Are the animal models appropriate (e.g., age and maturity) for the development of the LA-DDS proposed? If included, is the approach to determine target user preferences for a long-acting drug delivery system (either from prior studies in related populations or proposed in the target population including caregivers as appropriate) appropriate to inform the development of the product for this population?  Does the proposed collaboration with industry provide a feasible research approach to address the goals and objectives of the FOA?

 

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?

Specific to this FOA

Does the applicant have access to non-human primate facilities with infant and juvenile animals and/or a breeding program?

Additional Review Criteria
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.

 

Milestones

Are the milestones appropriate, adequately described, feasible, quantifiable and achievable within the proposed timeframe for the research elements they support? Are the milestones well-integrated into the research strategy?   

 

For research that involves human subjects but does not involve one of the 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 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.

 
Individuals Across the Lifespan

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 individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

 

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

 

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

 

Not Applicable

 

Not Applicable

 

Not Applicable

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

 

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

 

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

 

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

 

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

 

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

2. Review and Selection Process

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

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities More information is provided at Award Conditions and Information for NIH Grants

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award
Not Applicable

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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

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

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
Application Submission Contacts
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten on-time submission, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application processes and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Judi Miller
National Institute of Allergy and Infectious Diseases (NIAID)

Telephone: 240-292-4801
Email: jmillera@niaid.nih.gov    

Peer Review Contact(s)

Robert Freund, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-1050
Email:  freundr@csr.nih.gov 

Financial/Grants Management Contact(s)

Jenna Briggs
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-5137
Email: jenna.briggs@nih.gov     

Section VIII. Other Information

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.
Authority and Regulations
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.


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