Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Mental Health (NIMH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute on Drug Abuse (NIDA)
National Institute of Neurological Disorders and Stroke (NINDS)

Funding Opportunity Title

HIV Infection of the Central Nervous System (R01)

Activity Code

R01 Research Project Grant

Announcement Type

Reissue of PA-07-089

Related Notices

  • February 11, 2014 - This PA has been reissued as PA-14-094.
  • May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.

Funding Opportunity Announcement (FOA) Number

PA-11-014

Companion FOA

none

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestics Assistance (CFDA) Number(s)

93.242, 93.273, 93.279, 93.853

FOA Purpose

The National Institute of Mental Health (NIMH), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Drug Abuse (NIDA), and the National Institute of Neurological Disorders and Stroke (NINDS) invite research grant applications focused on defining the pathogenic mechanisms involved in Human Immunodeficiency Virus (HIV)-1 Associated Neurocognitive Disorders (HAND) and identifying therapeutic strategies to treat and prevent the neurobehavioral and neurological effects of HIV-1 on the central nervous system (CNS).  Applications ranging from basic research to clinical diagnosis and treatment in domestic and international settings are of interest.  Multidisciplinary research teams and collaborative alliances are encouraged but not required.

Key Dates
Posted Date
Open Date (Earliest Submission Date)

December 7, 2010

Letter of Intent Due Date

Not Applicable

Application Due Date(s)

Not Appllicable

AIDS Application Due Date(s)

Standard dates apply.

Scientific Merit Review

Standard dates apply .

Advisory Council Review

Standard dates apply

Earliest Start Date(s)

Standard dates apply

Expiration Date

January 8, 2014

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (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

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The National Institute of Mental Health (NIMH), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Drug Abuse (NIDA), and the National Institute of Neurological Disorders and Stroke (NINDS) invite research grant applications focused on defining the pathogenic mechanisms involved in Human Immunodeficiency Virus (HIV)-1 Associated Neurocognitive Disorders (HAND) and, identifying therapeutic strategies to treat and prevent the neurobehavioral and neurological effects of HIV-1 on the central nervous system (CNS).  Applications ranging from basic research to clinical diagnosis and treatment in domestic and international settings are of interest.  Multidisciplinary research teams and collaborative alliances are encouraged but not required.

Background

The prevalence of HAND remains high despite widespread use of antiretroviral therapy.  A recently completed large epidemiologic study by the CHARTER (CNS HIV Anti-retroviral Effects Research) group examined 1,574 participants cross-sectionally and 657 participants longitudinally and has reported a HAND prevalence rate of greater than 50% in HIV infected individuals in the United States.  Recent studies are showing that the phenotype of neurologic and neurocognitive complications are evolving in the era of highly active antiretroviral therapy (HAART).  In an effort to accurately classify recently observed phenotypic changes, a revised American Academy of Neurology definitional criteria for HAND was adopted.  The categories of HAND include Asymptomatic Neurocognitive Impairment (ANI), Mild Neurocognitive Disorder (MND), and HIV-Associated Dementia (HAD).  In the current treatment environment, MND is most prevalent, yet recent studies demonstrate that even mild neurocognitive deficits can interfere with activities of daily living and reduce quality of life in long-standing aviremic HIV-positive patients.  These clinical data inform the need for further research aimed at improving or preserving neurocognitive function in the presence of long term antiretroviral therapy.

Extensive research is ongoing to understand the molecular mechanisms of HIV neuropathogenesis.  HIV-1 infected macrophages and microglia appear to contribute to neurological injury through release of various factors, including viral gene products, such as Tat, Vpr and Nef, and proinflammatory cytokines, such as TNF-alpha, eicosanoids, nitric oxide, platelet activating factor, quinolinic acid and extracellular matrix degrading-proteases.  Viral proteins and host factors from activated macrophages, in turn, can activate astrocytes leading to the release of chemokines and cytokines such as CCL-2, SDF-1 and RANTES.  Neuronal loss, detected at autopsy in HIV-infected patients, is thought to occur through bystander effects, reactive oxygen species-mediated damage to cells and, likely results from apoptosis.  Morphologic studies demonstrate synaptodendritic degenerative changes with significant loss of synapses, decreased numbers of dendritic branches, and retraction of dendritic spines.  While much has been learned in the last two decades regarding the pathogenic processes involved in HIV-associated CNS disease, there are several gap areas related to the functional implications of these neurological changes and the novel pathophysiological mechanisms driving HAND in the HAART era.  Despite excellent viral control in the CNS, low level replication in specific brain regions, chronic inflammation, and changes in brain anatomy and homeostasis are likely to play pivotal roles in the expression of HAND.

Viral genetic variation impacts the development of HIV neuropathogenesis by altering neurovirulence, neurotropism, cell type specific and regional compartmentalization, CNS trafficking, and discordant viral evolution in the brain.  For example, sequence studies of HIV strains derived from brains of HAND patients identified a variant in the CD4 binding region of HIV gp120 which may confer increased macrophage tropism and risk for dementia.  Therefore, highly macrophage tropic viruses may represent neurotropic or neurovirulent viruses.  Additional studies have identified sequence variation in the C/EBP binding site of the HIV LTR which has been associated with brain-derived viral DNA from patients with HAND.  Additional research is needed to define the functional and neurobiological consequences of such viral genetic variation.

Discordant compartmentalized viral evolution in the CNS may also have an impact on disease course.  Phylogenetic analysis of HIV-Nef, gp120 and gp41 sequences from demented and non-demented cases have shown a relationship between HIV-1 evolutionary patterns in the brain and different neuropathologies.  Furthermore, viral evolution in the CNS may also have adaptive significance since recent studies also demonstrated divergence between lymphoid and brain derived HIV-1 Nef genes. 

Geographic differences in rates of HAND have been reported and hypothesized to reflect differences in the relative degree to which viral clades promote neuropathogenesis.  A recent study in Uganda has indicated that HIV-1 clades may function differentially to impact the clinical manifestations of HAND; clade D was found to be associated with an increased risk of dementia in HIV-infected patients when compared to clade A.  Although clade-specific promoter polymorphisms have been attributed to tissue specific viral replication in the periphery and HIV-1 Tat proteins have been studied with respect to differential clade effects on HAND, the molecular and genetic mechanisms involved in the impact of HIV clade diversity on neuropathogenesis in the CNS needs further study. 

In addition, variants in several host genetic factors have been reported to impact the pathophysiology of HAND.  For example, the homozygosity of the MCP-1-2578G-allele was associated with 50% reduction in risk of HIV infection.  However, once infected the same genotype was associated with accelerated disease progression and 4.5 fold increased risk of HIV-Associated Dementia (HAD).  The APOE-epsilon4 allele has been shown to be associated with increased risk of cognitive deficits, whereas the MBL-2O/O genotype was associated with an increased risk of cognitive decline in Chinese individuals infected with HIV.  Studies with the SIV model have shown that particular MHC class I alleles play a major neuroprotective role in lentiviral-induced CNS disease.  Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction than Mane-A*10 negative animals.  Other genes may be involved in host cell restriction in a cell type specific manner.  For example, the recently identified brain specific factor FEZ1 appears to represent a unique neuron-specific determinant of cellular susceptibility to infection in a cell type that is naturally resistant to HIV-1. 

Given that both viral and host genetic contributions have advanced our understanding of HAND, new genetic technologies may complement this effort, provide unique perspectives on the neuropathology, and aid in the identification of innovative strategies for the discovery of therapeutic drug targets to prevent, or interfere with, progression of HAND.  The use of state-of-the-art genetic approaches (including transcriptomics, phenomics, epigenomics, single genome sequencing, whole genome association studies, ultra-deep sequencing, exome sequencing, and systems biology) as well as the use of human sample resources and animal model systems are encouraged to study, and validate, viral and host genetic contributions to HIV neuropathogenesis. 

Another critical issue that is of emerging interest is the interaction of chronic HIV infection, living with HAART long term, and aging associated neurodegenerative processes.  The Center for Disease Control has indicated that the number of persons aged 50 years and older living with HIV/AIDS is increasing and derives from two subpopulations:  (1) HIV-diagnosed cases of a “younger group” surviving into older age because of the efficacy of HAART in reducing mortality; and (2) newly HIV-infected cases of an “older group.”  As a result of this major demographic shift there is an urgent need to better define the underlying pathophysiology of neurological complications and neurocognitive decline in the HIV infected aging populations.

Another key area of focus of this initiative is to develop therapeutic strategies for HAND.  These therapeutic strategies include the development of optimal antiretroviral therapies.  It is worth noting that there is controversy in the field as to the importance of generating better CNS penetrating antiretrovirals.  Recent studies reveal the possible neurocognitive benefits of high central nervous system penetration effectiveness (CPE) ranking regimens and treatment initiation at CD4 counts more than 350/uL.  However there is also evidence of the neurotoxic effects of antiretroviral therapy.  In addition to less toxic anti-viral approaches, novel therapeutics including immunomodulatory or neuroprotective strategies need to be identified and developed to address the chronic inflammation and neurobiological changes that are central features of this disease. 

Chronic exposure to drugs of abuse, as well as co-infections and co-morbidities that are prevalent in drug using populations, present unique challenges for HIV prevention and treatment and are likely to affect host-virus interaction and disease progression, particularly in the brain and the immune system. The role of drug abuse in fueling the HIV/AIDS epidemic has evolved. While the number of new infections associated with injection drug use has decreased, there is a need to understand how non-injection substance abuse impacts different aspects of infection and disease progression.  While it is difficult to separate effects of substance abuse on antiretroviral treatment adherence from direct biological effects, experimental evidence suggests that substances such as methamphetamine, cocaine, opioids and cannabinoids may impact HIV infection, replication, and CNS disease progression.  Innate and adaptive immune responses, blood-brain barrier integrity, and CNS homeostasis can be affected by substance abuse as well as withdrawal, and these changes have the capacity to affect HIV-associated disease progression in the CNS, particularly as patients are living longer.  More research is needed to elucidate the biological interactions between chronic exposure to drugs of abuse, as well as the neurotransmitter systems and physiological changes involved in addiction, with HIV infection of the CNS and HAND. Studies that address these interactions and define causal relationships with the behavioral and cognitive deficits are of interest.

In summary, the goals of this FOA are to stimulate further research on delineating the pathophysiology of HAND in the setting of long-term HAART and identify potential targets for novel therapeutic strategies in domestic and international settings.  Applications ranging from basic research to clinical diagnosis and treatment are of interest.  Multidisciplinary research teams and collaborative alliances are encouraged, but not required. 

Areas of Research Interest

The research areas that are pertinent to this FOA include, but are not limited to:

Evolving Mechanisms of HIV Neuropathogenesis in the HAART era

HIV Neuropathogenesis during Acute and Early Stages of Infection

Viral and Host Genetics

Neuroimaging Studies

Use of neuroimaging approaches such as magnetic resonance spectroscopy (MRS), positron emission tomography (PET), magnetic resonance imaging (MRI), functional MRI (fMRI), blood oxygenation level dependent functional magnetic resonance imaging (BOLD fMRI), diffusion tensor imaging (DTI), arterial spin-labeling MRI (ASL-MRI) and chemical shift imaging to:

Aging and HAND

Therapeutics

Animal Models and Specimen Resources

The NIAAA will consider applications to this Program Announcement that are relevant to the mission of the institute, such as investigations of the co-morbid effects of alcohol use and abuse on mechanisms of HIV infection of the central nervous system.

Section II. Award Information
Funding Instrument

Grant

Application Types Allowed

New
Renewal
Resubmission
Revision

The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.

Award Budget

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds.

Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation; see NOT-OD-05-004.

Award Project Period

The maximum period is 5 years.

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:

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

Nonprofits Other Than Institutions of Higher Education

For profit Organizations

Governments

Other

Foreign (non-U.S.) components of U.S. Organizations are allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Eligible Individuals (Project Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) 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 SF 424 (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.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

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, 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.

Required and Optional Components

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

Page Limitations
PHS 398 Research Plan Component

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

Resource Sharing Plans

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS) Sharing Plan) as provided in the SF424 (R&R) Application Guide.

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 with the following modification:

Foreign Organizations

 Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations 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 in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via 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.

Applicants are responsible for viewing their application 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 SF 424 (R&R) Application Guide.  Paper applications will not be accepted.

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(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.

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 Central Contractor Registration (CCR). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

In order to expedite review, applicants are requested to notify the appropriate IC Referral Office when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Foreign Applications (Non-domestic [non-U.S.] Entities)

Indicate how the proposed project has specific relevance to the mission and objectives of the NIH/IC and has the potential for significantly advancing the health sciences in the United States.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF 424 (R&R) Application Guide.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

Overall Impact

Reviewers will provide an overall impact/priority 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?

Investigator(s)    

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

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? 

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

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

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/priority score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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/priority score.

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s)  (assignments will be shown in the eRA Commons), in accordance with NIH peer review policy and procedures, using the stated review criteria.

As part of the scientific peer review, all applications will:

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 . 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:

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 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.

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.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts

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

Application Submission Contacts

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Jeymohan Joseph, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: (301) 443-6100
Email: jjeymoha@mail.nih.gov

John A. Matochik, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone:  (301) 451-7319
Email:  jmatochi@mail.nih.gov

Diane M. Lawrence, Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: (301) 594-3225
Email: lawrencedi@nida.nih.gov

May Wong, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1431
Email: mw132k@nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: (301) 443-2805
Email: siscor@mail.nih.gov

Judy S. Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone:  (301) 443-4705
Email:  jfox@mail.nih.gov

Suezette Epps
National Institute on Drug Abuse (NIDA)
Telephone: (301) 443-6710
Email: eppss@mail.nih.gov

Ms. Tijuanna DeCoster
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9531
Email:Tijuanna.DeCoster@ninds.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 Parts 74 and 92.


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