Department of Health and Human Services

Part 1. Overview Information

Key Dates

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.

Table of Contents

1. Part 1. Overview Information
2. Part 2. Full Text of the Announcement
   1. Section I. Funding Opportunity Description
   2. Section II. Award Information
   3. Section III. Eligibility Information
   4. Section IV. Application and Submission Information
   5. Section V. Application Review Information
   6. Section VI. Award Administration Information
   7. Section VII. Agency Contacts
   8. Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to solicit innovative research applications that seek to advance the development of bioanalytical assays, pill ingestion sensors, drug metabolite and taggant detection systems, or wireless technologic approaches for monitoring and improving adherence to oral antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP).

Background

The challenge of sustaining adherence to oral medication regimens has long vexed chronic disease prevention and management efforts/programs. Adherence to antiretroviral therapy (ART) is critical for achieving viral suppression, yet observational studies indicate that ART adherence can decline over time and is often punctuated by short treatment interruptions that predict viral breakthrough. Adherence is also a concern for the HIV prevention domain. The HIV prevention efficacy of oral pre-exposure prophylaxis (PrEP) is highly contingent on adherence, but data show highly variable adherence levels and patterns among participants in blinded and open-label PrEP trials.

Valid measurement of oral antiretroviral (ARV) medication adherence is critical to both clinical trials and clinical care in HIV treatment and prevention. In research, proof-of-concept trials testing new pharmacologic regimens require valid adherence data for proper interpretation, because any null findings may stem from poor adherence rather than a lack of drug efficacy. In clinical care, adherence monitoring can help optimize treatment and prevention outcomes by facilitating delivery of support interventions to those in need.

There is no gold standard for oral ARV adherence measurement. Available methods include self-report, pharmacy refill measures, announced and unannounced pill counts, electronic drug monitoring, and drug concentrations. The validity and precision of these tools vary, and each affords a different set of advantages and disadvantages depending upon the context of its use.

Innovations to advance the validity and capabilities of ARV adherence measures could help researchers and clinicians accurately diagnose and rapidly address non-adherence to improve HIV prevention and care outcomes. Adherence measures could be strengthened in highly novel ways that include the provision or assessment of:

• Evidence of medication ingestion. Existing adherence measures generally infer rather than document the actual ingestion of oral medication. Approaches providing direct confirmation of medication ingestion avoid a number of threats to the validity of many adherence measures, including social desirability concerns and memory biases.
• Longitudinal patterns of adherence. Few adherence measures allow ready assessment of temporal patterns in medication taking-behavior. Discerning temporal adherence patterns permits identification of lower/higher adherence periods, adherence gaps, and associated contextual determinants. Longitudinal information on adherence is also important for circumventing the "white coat" effect (improved adherence just prior to clinic appointments).
• Real-time adherence monitoring. Existing adherence measures are retrospective by definition and typically discern adherence problems many weeks or months after they have occurred. Real-time monitoring allows for assessment of adherence behavior as it occurs in ecologic settings and provides the ability to intervene on non-adherence before it may compromise prevention and treatment outcomes.
• Individual feedback on adherence performance. Research suggests that feedback on adherence performance can be a potent component of adherence support interventions. Feedback on adherence performance can be rewarding for individuals with good adherence and enlightening for those unaware of suboptimal adherence. Adherence performance data also provides actionable information for the targeted delivery of adherence interventions.

Many historic research innovations in adherence measurement have been made in the HIV/AIDS field. This funding opportunity continues that tradition by inviting development and testing of the next generation of adherence measures.

Objectives

This FOA invites innovative research applications for assay or technology development that could serve as valid measures of adherence to antiretrovirals (ARVs) prescribed for HIV treatment or prevention. These assays, technologic tools or devices should be developed to monitor ARV adherence in routine clinical practice, in field studies, or in the context of a clinical trial designed to measure efficacy. The goal is to improve the validity of adherence data, provide actionable adherence information to patients and their clinical providers, and create timely opportunities to intervene upon observed non-adherence before HIV treatment or prevention outcomes are compromised.

An ideal assay, device or tool developed or used in research supported by this FOA would possess the following characteristics:

• indicate that oral medication ingestion occurred;
• offer real-time monitoring of adherence behavior in ecologic settings;
• allow for discernment of longitudinal patterns of adherence; and
• provide timely feedback on adherence patterns so that HIV preventative and therapeutic outcomes can be optimized.

The ideal assay, device, or tool for monitoring ARV adherence will address all or most of these characteristics. However, a research approach that addresses fewer characteristics but uses highly innovative approaches could meet the objectives of this FOA.

Specific Areas of Research Interest

This FOA will support the development of assays, devices, or monitoring tools and clinical studies to validate their use in measuring ARV adherence. Early-stage clinical trials designed to examine feasibility, acceptability, and the preliminary impact on ARV adherence can also be supported.

Applicants are encouraged to test feasibility and acceptability in populations known to be challenged by adherence, such as those with mental health disorders or adolescents. Clinical populations in the United States or international settings may be appropriate for research proposed under this FOA.

Examples of projects of interest under this FOA include:

• Development and validation of ARV metabolite assays in clinical specimens followed by feasibility and acceptability testing in a clinic population.
• Development and validation of medication taggants followed by feasibility and acceptability testing in a clinic population.
• Prospective studies that test feasibility and acceptability of ARV adherence monitoring approaches that provide confirmation of oral medication ingestion through ingestion sensors or other metabolite detection systems.
• Advances in technologic approaches providing real-time electronic monitoring of ART or PrEP adherence behavior and delivery of automated interventions in response to observed adherence performance.
• Research that compares multiple methods for prospective monitoring of ART or PrEP adherence behavior in terms of acceptability, feasibility, cost, precision, ability to catalyze timely interventions for non-adherence, or impact on behavioral adherence or drug detection.
• Interventions designed to incentivize ARV adherence with prospective monitoring of adherence behavior or outcomes.
• Interventions which triage patients to different levels of intervention intensity based on observed need during prospective adherence monitoring.

Non-responsive Areas of Research

Applications proposing any of the following research topics will be identified as non-responsive and will not be reviewed.

• Clinical trials designed to test efficacy or effectiveness in improving adherence behavior
• Research focusing exclusively on self-reported measures of adherence (via questionnaires, text messages, etc.).
• Electronic drug monitoring devices that lack wireless capacities.
• Use of assays that involve invasive specimen collection (e.g., tissue biopsies, collection of cerebrospinal fluid) that would impact acceptability to patients.
• Studies focusing exclusively on clinic- or home-based pill count approaches to adherence assessment.

Applicants are strongly encouraged to contact the Scientific/Research Contact(s), listed in Section VII of this FOA, to discuss the appropriateness of the scope of the proposed project.

Monitoring Clinical Studies and Clinical Trials

The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies and/or clinical trials to ensure the safety of participants and the validity and integrity of the data. The NIH policies on data and safety monitoring specify that the level and frequency of monitoring should be commensurate with the risks, nature, and complexity of the clinical research, and are in addition to any monitoring requirements imposed by FDA or the NIH Guidelines for Research Involving Recombinant DNA Molecules ("NIH Guidelines"). More information on NIH Policies and Institute/Center Guidance for Data and Safety Monitoring of Clinical Trials is available at: http://grants.nih.gov/grants/policy/hs/data_safety.htm.

Section II. Award Information

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.

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.
  • 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.

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

Number of Applications

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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept 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.

Section IV. Application and Submission Information

1. Requesting an Application Package

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.

2. Content and Form of Application Submission

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

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

Letter of Intent

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
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5049
Email: [email protected]

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 , with the following additional instructions:

Other Attachments: The following information must be submitted as an attachment entitled "Regulatory.pdf" if the application proposes a project using a taggant or ingested sensor as an adherence measure.

• Applications where regulatory status is known: Clearly specify the device’s regulatory status with the US Food and Drug Administration (FDA) or with another relevant regulatory authority (e.g., approved for use, or listed as "Generally Recognized as Safe" for oral ingestion). Include the following in clearly marked sub-sections of the document: Clinical Protocol Synopsis and Data Safety and Monitoring Plan.
• Applications where regulatory status will be determined during the grant period of performance: Clearly describe the experience and capability needed to develop regulatory submissions to the FDA or other regulatory body. Include the following in clearly marked sub-sections of the document: Clinical Protocol Synopsis and Potential Risks to Subjects for Safety Monitoring.

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

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:

Research Strategy: As part of the Research Strategy, applicants should clearly describe how the assay, device, or tool for monitoring ARV adherence will address all or most of the following characteristics:

• Indicate that oral medication ingestion occurred;
• Offer real-time monitoring of adherence behavior in ecological settings;
• Allow for discernment of longitudinal patterns of adherence; and
• Provide timely feedback on adherence patterns so that HIV preventative and therapeutic outcomes can be optimized.

Applicants must include a realistic Management Plan with milestones and timelines. This plan should outline any pre-clinical development of the bioanalytical adherence assay or monitoring tool, if applicable. If a pilot study is proposed, plans for construction of the adherence strategy and design and implementation of one or more pilot studies to evaluate the acceptability and feasibility of the strategy, its validity, or its preliminary impact on ARV adherence, must be included. If an applicant proposes to use a taggant, assay or device that would be regulated by the US FDA, steps of a regulatory strategy should also be part of the Management Plan.

Applications that involve development of laboratory assays to use as indicators of adherence to specific antiviral drugs must specify which oral antiretroviral(s), active metabolites and/or other markers will be detected. The advantages of the choice of drug (compared to other drugs) as a proposed adherence measure in a specific population must also be discussed. Assays to be developed can be qualitative (present/absent), semi quantitative, quantitative, or an algorithm of multiple assays. Applicants must describe the samples that will be used to develop, test, and validate the assay and elaborate on how sample collection, processing and storage will likely be acceptable and feasible in clinical and non-clinical settings and minimally burdensome to patients (e.g. blood, saliva, hair, urine). Assessments of inter- and intra- individual variability and dose proportionality are encouraged.

Applications that describe the development of an assay, device, or tool to measure adherence must describe the processes of validation of the measure and also how the measure will be tested for feasibility and acceptability in a target population.

If FDA oversight would be required for testing the product in humans, the applicants are strongly encouraged to discuss their regulatory strategy prior to submission with the appropriate Scientific/Research contacts listed in Section VII at the end of this FOA. This strategy should include a general plan for regulatory sponsorship and a summary of product results in pre-clinical and pilot testing available to date.

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

• All applications submitted for the January 25, 2015, due date or after are expected to comply with the NIH Genomic Data Sharing Policy as detailed in NOT-OD-14-111, as applicable.
• 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.

Planned Enrollment Report

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

PHS 398 Cumulative Inclusion Enrollment Report

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

Foreign Institutions

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. Submission Dates and Times

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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. 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.

6. 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.

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 NOT-OD-13-030.

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.

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.

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?

To what extent does this project significantly advance the FOA's objectives to develop adherence measurement tools with the following characteristics: indicate that oral medication ingestion occurred; offer real-time monitoring of adherence behavior in ecologic settings; allow for discernment of longitudinal patterns of adherence; and provide timely feedback on adherence patterns so that HIV preventative and therapeutic outcomes can be optimized?

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?

If the project includes determining the regulatory status of a taggant or ingested sensor during the course of the grant period, has the investigator's experience and capability to develop regulatory submissions to the FDA or other regulatory body been clearly described?

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?

Does the application provide an adequate description of samples that will be used to develop, test, and validate the assay? Are the proposed sample collection, processing and storage likely to be acceptable and feasible in clinical and non-clinical settings as well as minimally burdensome to patients (e.g. blood, saliva, hair, urine)?

Are the methods for validation of the proposed adherence measure and how the adherence measure will be tested for feasibility and acceptability in the target population adequate?

Does the application provide a realistic Management Plan with appropriate milestones and timelines? If an applicant proposes to use a taggant, assay or device that would be regulated by the US FDA, has aregulatory strategy been included in the Management Plan?

If the project includes a taggant or ingested sensor as an adherence measure, does the application provide information that clearly specifies the device’s regulatory status with the US Food and Drug Administration (FDA) or with another relevant regulatory authority (e.g., approved for use, or listed as "Generally Recognized as Safe" for oral ingestion)?

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?

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?

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.

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

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.

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) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) the National Institute of Allergy and Infectious Diseases, 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 on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

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.

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

Section VI. Award Administration Information

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.

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 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.

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 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
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
Email: [email protected]

Scientific/Research Contact(s)

Vanessa Elharrar M.D., M.P.H.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-292-4787
Email: [email protected]

Michael Stirratt, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 240-627-3875
Email: [email protected]

Peer Review Contact(s)

Peter R. Jackson
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5049
Email: [email protected]

Financial/Grants Management Contact(s)

Ann Devine
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2988
Email: [email protected]

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: [email protected]

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 Parts 74 and 92.