Part I Overview Information


Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
National Institute on Alcohol Abuse and Alcoholism (NIAAA), (http://www.niaaa.nih.gov)

Title:  Mechanisms of Nervous System Dysfunction: Impact of Alcohol Abuse on HIV-1 Neuropathogenesis (R01)

Announcement Type
New

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV.

Request for Applications (RFA) Number: RFA-AA-07-015

Catalog of Federal Domestic Assistance Number(s)
93.273

Key Dates
Release/Posted Date: March 12, 2007
Opening Date:   April 14, 2007 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date: April 14, 2007
NOTE: On time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization). 
Application Submission/Receipt Date:  May 11, 2007
AIDS Application Submission/Receipt Date: May 11, 2007
Peer Review Date: July/August 2007
Council Review Date: October 2007
Earliest Anticipated Start Date: September 15, 2007
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: May 12, 2007

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives


Section II. Award Information

1. Mechanism of Support

2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants

    A. Eligible Institutions
    B. Eligible Individuals
2. Cost Sharing or Matching
3. Other-Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information

2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Submission, Review, and Anticipated Start Dates
          1. Letter of Intent
    B. Submitting an Application Electronically to the NIH
    C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Sharing Research Data
    D. Sharing Research Resources
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices

2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contacts
1. Scientific/Research Contact(s)

2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

This Funding Opportunity Announcement (FOA), issued by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, solicits Research Project Grant (R01) applications from institutions/organizations to determine the impact and interactions (additive or synergistic effects) of alcohol abuse and addiction on the basic mechanisms underlying the onset, development and progression of central and peripheral nervous system disorders and complications resulting from HIV-1 infection. HIV-1 infection causes mild motor and cognitive deficits to severe dementia in the central nervous system, and sensory neuropathies peripherally. While disease is associated with nervous system infiltration of activated macrophages and the development of HIV-encephalitis (HIVE), the neuronal deficits result largely from the detrimental actions of viral and host factors on neurons and neuronal function. Thus, the intent of this FOA is to encourage applications that will determine the effects of abusive alcohol consumption on the abilities of viral-encoded proteins and/or host factors to cause the neuronal dysfunction and damage that produces HIV-associated neurological complications. Research studies may be proposed at the genetic, molecular, cellular or systems levels of analyses, and could include areas such as gene expression studies, perturbations of mitochondrial function and cytokine signaling pathways, neuron or glial cell function, excitability and communication, and neuroimaging approaches that study changes in brain metabolism, neurochemistry and neuropharmacology as relevant for understanding the mechanisms underlying the etiology and pathogenesis of neuronal, cognitive, motor and behavioral decline. It is expected that applications will employ human subjects or animal models (simian, feline, rodent) that are readily translatable to the human condition. Proposals to study the effects of alcohol consumption on viral replication, viral entry into the nervous system, and increased viral-mediated neuroinflammation are not considered responsive to this FOA. Applicants proposing research studies that are outside the intent of this FOA may consider responding to PA-07-089; HIV Infection of the Central Nervous System (R01).

Background

In October 2006, the NIAAA convened a meeting of its Extramural Advisory Board to review the HIV/AIDS research portfolio and develop future directions for HIV-related biomedical research. One recommendation was to focus research on key mechanistic targets for ethanol and HIV-induced injury to identify, measure and prevent additive and interactive harmful effects at the cellular and organ systems level, including brain injury and disease. The introduction of highly-active antiretroviral therapy (HAART) has been effective in enhancing the quality of life of those individuals infected with HIV-1 by attenuating the progression to and the medical consequences of AIDS. Unfortunately, the neurological complications associated with HIV-1 infection continue to be significant causes of morbidity and mortality in infected individuals. The neurological impairments produced by HIV-1 infection within the brain and central nervous system range from minor motor and cognitive abnormalities, generally termed minor cognitive-motor disorder (MCMD), that usually occur in the early stages of viral infection and are more prevalent because of HAART, to fully expressed HIV-associated dementia (HAD) occurring in the later stages of disease. Within the peripheral nervous system, the two common forms of HIV-associated sensory polyneuropathies are distal symmetric polyneuropathy (DSP) that usually occurs with advanced HIV-1 infection, and antiretroviral toxic neuropathy (ATN) that results from neurotoxicity caused by antiretroviral therapy. Central nervous system deficits affect more than 25% of HIV-infected individuals. Additionally, the incidence of HIV-1 associated peripheral neuropathies is 30-40%, yet the prevalence of neuropathy and other peripheral nervous system deficits as determined at autopsy is closer to 100%. Complicating this picture is that higher rates of alcohol consumption have been reported among HIV positive (HIV+) individuals as compared with the general population. For example, the prevalence of hazardous alcohol consumption among HIV+ individuals has been estimated to be as high as 28% in the United States, and to be much greater - perhaps in excess of 80% - in international settings. Alcohol consumption plays a detrimental, but incompletely defined, role in the pathogenesis of HIV-associated neurological disease because most studies of HIV neuropathogenesis have ignored the contributions of alcohol abuse as a factor in disease onset, development and progression. Therefore, there is a need to understand the interactions and impact of alcohol abuse and addiction (alcoholism) to the development and progression of the neurological complications resulting from HIV-1 infection.

Neurological Damage and Deficits

Structural damage: The impact of alcoholism on HIV-associated neurological disease is controversial. Within the central nervous system, studies have documented both additive and synergistic effects of viral infection and alcoholism on brain pathology. Both gray matter and white matter are damaged independently by HIV-1 infection or detrimental alcohol consumption. The damaging effects on gray matter structure are brain-region specific, indicating that there are regional variations and sensitivities towards exposure to viral infection or alcoholism in producing neuronal injury and atrophy. However, disruption of white matter integrity and demyelination produced by either HIV-1 infection or alcoholism occurs ubiquitously throughout the brain. Furthermore, many of the same brain regions, in particular, the frontal lobes, corpus callosum, basal ganglia, brainstem, and cerebellum, are damaged by either HIV-1 infection or alcoholism. Synergistic effects of alcoholism on HIV-produced brain damage have been observed towards ventricular enlargement, callosal thinning, and degradation of corpus callosum macro and microstructure. 

Both HIV-1 infection and alcoholism can cause sensory neuropathies within the peripheral nervous system. The prominent pathological feature of DSP and ATN is distal axonal degeneration of unmyelinated fibers. Similarly, the main pathological feature of alcoholic polyneuropathy is distal axonal degeneration involving both myelinated and unmyelinated fibers. While alcoholism is a risk factor for the development of HIV-associated sensory polyneuropathies, the additive or synergistic interactions of HIV infection and alcoholism on peripheral nervous system structure have not been studied.

Functional deficits: HIV-1 infection or alcoholism, independently, can produce cognitive, motor and behavioral deficits within the brain and central nervous system, especially during the later stages of HIV-1 disease or in current, heavy drinkers. Unfortunately, studies on the additive or synergistic effects of alcoholism on the neuropsychological deficits and impairments resulting from HIV-1 infection have been somewhat problematic as these studies have been confounded by such factors as the pattern, frequency and volume of alcohol drinking, by age, and by adherence to antiretroviral therapy. Despite these limitations, additive effects of HIV infection and alcoholism have been reported in producing deficits of attention, memory, and reaction time, and synergistic interactions have been reported on motor and visuomotor functioning.

The clinical symptoms of HIV-associated sensory (DSP and ATN) and alcoholic polyneuropathies are similar. Each disease express as pain and burning sensations that begin in the toes and feet, and progress up the legs. Although it is known that alcoholism is a major risk factor for the development of HIV-associated sensory polyneuropathy, the mechanistic actions of alcoholism that promote HIV-associated peripheral dysfunction and pain are unknown.

Mechanisms underlying the Neurological Complications produced by HIV Infection or Alcohol Dependence

Pathological and neuropsychological studies clearly show that HIV-1 infection and alcoholism produce similar structural and functional deficits within the nervous system. Thus, it may be expected that viral infection and alcoholism exert their effects through common mechanisms or pathways. Presently, there is scarce information on the mechanistic interactions between HIV-1 infection and abusive alcohol consumption in producing neuronal dysfunction and damage. The following represent areas of research of which it might be expected that alcohol could interact to facilitate or enhance the onset, development and progression of HIV-associated neurologic disease. This discussion is intended as a guide and is not meant to be exclusive of potential areas of research on the interactions and impact of alcoholism on the neurological complications that result from HIV-1 infection.

Viral proteins/host factors: The primary mediators of HIV-1 infection within the nervous system are activated perivascular and parenchymal macrophages and microglia that subsequently enter the brain, and to a lesser extent, brain astrocytes. Circulating activated macrophages and microglia also contribute to peripheral disease. Once in the nervous system, HIV-1 infection of these cells produces neurological impairments by altering cell secretory function leading to the overproduction and secretion of cytokines, chemokines, arachidonic acid derivatives, oxygen free radicals and excitatory amino acids. The release of these host factors may in turn promote apoptotic signaling or otherwise negatively affect other neuronal signal transduction pathways to alter neuronal function and produce neuron injury and death. In addition, soluble HIV-1 encoded proteins, such as Tat, gp120, and gp41, may have direct cytotoxic actions on neurons. The effects reported for these viral proteins include alterations of calcium homeostasis, NMDA-type glutamate receptor function, oxidative stress and apoptosis. The ability of viral-encoded proteins to affect the release of cytokines and chemokines, thereby increasing the ability of these agents to cause neuronal dysfunction and damage, has also been demonstrated.

Very few studies have addressed the mechanistic interactions between viral or host proteins and alcohol. A synergistic effect of alcohol on Tat-induced neurotoxicity acting through glutamatergic (NMDA-type glutamate receptor) hyperexcitability has been reported in hippocampal slice cultures. Alcohol has also been reported to potentiate gp120-induced apoptosis. It is expected that applications will propose studies on the mechanistic interactions between viral or host factors and alcohol on neuronal function and signal transduction pathways that contribute to neuronal dysfunction and damage leading to the development of HIV-associated neurological disease.

Oxidative stress/mitochondrial dysfunction: Increasing evidence supports a significant contribution of oxidative stress, leading to mitochondrial dysfunction and apoptosis, in the neuropathogenesis of HIV infection. For example, antioxidant therapy has been reported to slow the progression of the neurological complications resulting from HIV-1 infection. Among possible mechanisms, increased expression of inducible nitric oxide synthase (iNOS) and astrocyte apoptosis has been reported with HIV-associated neurological disease progression. The resulting overproduction of nitric oxide may produce damage by impairing the endogenous neuroprotective function of astrocytes. Peripherally, while the contributions of oxidative stress and mitochondrial dysfunction in the development of HIV-1-associated DSP are unknown, the cause of ATN appears to be through the ability of antiretroviral agents to cause mitochondrial dysfunction and energy failure.

Oxidative stress leading to mitochondrial dysfunction is thought to contribute to the development of alcohol-induced brain damage and altered neuronal function as well. Ethanol can induce oxidative stress through the formation of free radicals and reactive oxygen species (ROS), and by reducing intracellular antioxidant (glutathione) capacity.  The pro-oxidant effect of ethanol derives from its induction of cytochrome P450 2E1 (CYP2E1) and the subsequent formation of ROS. Alcohol exposure induces both microsomal CYP2E1 and also mitochondrial CYP2E1. In brain tissue, CYP2E1 is a major source of superoxides and other reactive oxygen species which are created as an integral part of the concurrent oxidation of alcohol (in the cytosol) and NADH (in the mitochondria).  Additionally, elevated amounts of CYP2E1 serve to increase the rate of alcohol metabolism.  The metabolism of alcohol by CYP2E1 likely also contributes to damage within the nervous system through the production of acetaldehyde, a highly reactive and toxic metabolite. Oxidative damage to the mitochondria itself can alter membrane permeability, membrane potential, calcium homeostasis, cause swelling and fractured cristae, leading to cytochrome c release, further ROS production, and eventually neuronal death through apoptosis. Accumulation of ROS such as superoxide, hydrogen peroxide, and hydroxyl radicals along with a compromised antioxidant capacity (alcohol exposure causes reduced levels of glutathione, an endogenous protective mechanism against the damaging actions of excess ROS) contribute to excess damage to cellular proteins, lipids, and nucleic acids which can lead to cell death in brain and other tissues. Catalase, xanthine oxidase, and nitric oxide superoxidase activities may also contribute to ethanol-induced oxidative stress within the nervous system.

A recent, emerging area of research is the regulation of mitochondrial function and cellular energetics by peroxisome proliferator-activated receptors (PPAR), especially the role of the PPAR coactivator-1 (PGC-1) family of transcriptional coactivators, particularly PGC-1. PPAR are nuclear receptors that relay physiological and nutritional cues to activate gene regulatory responses. These receptors appear to have a considerable role in the regulation of lipid metabolism, glucose homeostasis and cellular differentiation. PGC-1 coactivators interact with both nuclear receptor and non-nuclear receptor transcription factors to regulate mitochondrial biogenesis and increase mitochondrial energy production. Recently, evidence is finding that PGC-1 serves to monitor and control the production of ROS, thereby maintaining proper mitochondrial function. While little is known of the actions of HIV-1 infection or alcoholism on PPAR and its coactivators, PPAR agonists have been shown to have anti-inflammatory properties and to block HIV-1 replication in infected peripheral blood cells from HIV-infected subjects. In addition, modulation of pathways involving PPAR may improve the metabolic alterations produced by HAART.

Glutamate excitotoxicity: It has been proposed that HIV-associated neurological impairments may be caused through virus-produced alterations in host cell secretory function that results in the production and secretion of excitatory amino acids, such as glutamate. Increased amounts of available glutamate could hyper stimulate glutamatergic transmission thereby causing neuronal excitotoxicity. Viral-encoded proteins, such as Tat and gp120, may also directly activate glutamate receptors to cause neurotoxic damage.

Alcohol-induced brain damage has also been proposed to occur as a result of glutamate hyperexcitability. Alcohol inhibits glutamate (NMDA-type) receptors. In animal models, alcohol exposure causes a homeostatic up-regulation of NMDA-type receptors within the brain. Glutamate-induced excitotoxicity occurs as a consequence of over-stimulation of glutamatergic transmission during abrupt withdrawal from alcohol. Although there are very few studies, a synergistic effect of alcohol on Tat-induced neurotoxicity has been reported in hippocampal slice cultures. This neurotoxic effect was found to be mediated through activation of the NMDA-type glutamate receptor.

Human neuroimaging: Neuroimaging approaches are beginning to inform the pathology and pathogenesis of the neurological deficits caused by both HIV-1 infection and alcoholism. Structural imaging is showing that similar effects, and for some brain regions synergistic effects, are produced in brain pathology that results from HIV-1 infection and alcoholism. Functional imaging is further informing the neuronal damage and functional deficits due to HIV-1 infection and alcoholism. For example, measures of brain activity show reduced cerebral blood flow and glucose metabolism due to viral infection, especially in the early stages of disease, and to alcoholism. These effects are particularly evident in frontal brain regions. Positron emission tomography (PET) studies have found reduced levels of the dopamine transporter (DAT), but normal levels of the dopamine (DA) D2-type receptor in subcortical brain regions in individuals diagnosed with HAD. In alcoholic individuals, PET studies have reported decreased levels of both DAT and DA D2-type receptors.

Studies of brain metabolites through the use of magnetic resonance spectroscopy (MRS) are also reporting both similar and interacting effects of HIV-1 infection and alcoholism. Neurodegeneration and neuronal atrophy (injury or death of neurons and synapses) probably through their abilities to produce mitochondrial dysfunction, and increased gliosis and membrane turnover are observed with either HIV infection or alcoholism. Although studies addressing the interactions of HIV infection and alcoholism are few, it has been reported that HIV-1 infection and alcoholism produce an interactive effect on parietal-occipital structure. A cumulative, but not interactive, decrease has been observed in white matter metabolites. Although conflicting reports have been published, some evidence from MRS studies suggests that HAART may attenuate neuronal injury (observed as recovered N-acetyl aspartate and other metabolite concentrations) through improved mitochondrial function, yet has little effect on reducing glial cell proliferation. MRS studies have also reported partial reversal of alcoholism-induced neuronal damage with abstinence. Recovery of damage with abstinence occurs more prominently in white matter than in gray matter. Thus, neuroimaging approaches in humans or in well-defined animal models of HIV infection that determine changes in brain metabolism, neurochemistry, and neuropharmacology have the potential to contribute to our understanding of the interaction of alcoholism on the mechanisms of HIV neuropathogenesis.

Other research areas: HIV-1 infection within the nervous system causes the release of increased amounts of cellular host factors, and the production of viral-encoded proteins, that contribute to HIV-1 disease neuropathogenesis. In addition to the potential actions of these host and viral factors as discussed, these agents may have effects on additional protein components, neuronal excitability and signal transduction pathways that further contribute to the development of HIV-associated neurological deficits and disease. The actions of ethanol on nervous system function vary as well. Alcohol can alter nervous system function through its actions on neurotransmitter receptor systems, ion channels, or signal transduction pathways. Therefore, alcoholism may increase HIV-associate neurotoxicity by enhancing the mechanistic actions of cellular and viral factors on common proteins and biochemical pathways.

Malnutrition, vitamin (thiamin) deficiencies and alcoholic liver disease may occur as a result of chronic alcohol consumption. In addition to the direct actions of alcohol on the nervous system, it has been proposed that the metabolic and physiological consequences of these deficiencies and diseases may contribute to alcohol-induced brain neurotoxicity and functional deficits. Correspondingly, these consequences of alcoholism may also increase the risk of developing, or further enhance the progression of, HIV-associated neurologic disease.

Glial cells have a neuroprotective role as support cells to maintain and ensure proper nervous system function. Glial cells provide structure, monitor the environment to maintain neuron homeostasis, and act as scavengers of cellular debris. As an example, glutathione is produced by glia and functions as an endogenous scavenger and neuroprotectant against ROS damage. Chronic alcohol exposure has detrimental effects on normal glial cell function. Reduced glutathione levels are associated with abusive alcohol consumption, thereby increasing the risk of damage produced by oxidative stress. Therefore, alcoholism may contribute to the development of the neurological complications of HIV-1 infection by reducing the neuroprotective actions of glial cells. Alternatively, alcoholism may further impinge on the detrimental mechanistic actions of host and viral factors produced by HIV-1 infection to perturb glial cell function, and this is an area that needs to be studied.

Studies that focus on specific groups or populations may further inform our understanding of the impact of alcoholism on HIV-associated nervous system disease. For example, the interactions of alcoholism on the mechanisms that contribute to the development of HIV-associated neurological disorders in youth and adolescents may be unique from those occurring in the adult. HIV-1 infection in youth can produce cognitive and behavioral deficits generally diagnosed as HIV-1 associated progressive encephalopathy (PE). PE has a clinical presentation and course that differs from adult HAD. It has been suggested that this difference is due to unique effects of HIV-1 encoded viral proteins and secreted neurotoxic host factors on the developing brain and nervous system as compared to the adult, or to the manner in which the immature immune system responds to HIV-1 infection or treatment. The pattern of consumption and exposure to alcohol by youth may further contribute to differences in HIV-1 neurologic disease occurrence and progression. Adolescents who drink usually exhibit a binge pattern of alcohol consumption (they drink less frequently but consume larger amounts per episode) as compared with the more regular pattern of drinking by adult alcoholics. Proposals to study the interactions of HIV-1 infection and detrimental alcohol consumption on neurodevelopmental processes and hormone signaling in the maturing brain and nervous system are encouraged.

Applicants are further encouraged to propose studies that utilize human postmortem brain tissue to determine the mechanistic interactions and impact of alcoholism on HIV-induced neurologic disease. Tissue may be currently collected or obtained from existing brain banks and repositories. Postmortem brain tissue that includes information on neuropsychological status, stage of viral infection and history of alcohol use may provide mechanistic insights into the impact of alcoholism on HIV-associated neurological disorders.

Research Areas of Interest

Currently, there is limited understanding of the basic mechanisms that underlie the development of neurological disease produced by HIV-1 infection, and which may be further exacerbated by excessive alcohol drinking. It is expected that a better understanding of the basic mechanisms underlying neuronal/glial cell dysfunction and the neuropathogenesis of HIV-associated nervous system disease, and of the impact and interactions of alcohol abuse and addiction in fostering and furthering neuronal dysfunction and damage underlying HIV-1 neuropathogenesis, will ultimately lead to the development of pharmacological therapies for treatment of the neurological complications of AIDS in patients who abuse alcohol.

Examples of research topics that are pertinent to this FOA include, but are not limited to:

CNS Damage and Dementia

Applications should address the neurobiological mechanisms impacted by alcohol exposure within the brain and central nervous system at the genetic, molecular, cellular and systems levels that contribute to the development of HIV-associated dementia (HAD) or its milder forms. Relevant areas may include:

HIV-associated Sensory Neuropathy

Applications should address the additive or synergistic mechanisms by which alcohol abuse and dependence further contribute to the development and progression of sensory polyneuropathies within the peripheral nervous system caused by HIV-1 infection or by antiretroviral treatment for HIV-1 infection. Relevant areas may include:

As appropriate for understanding the mechanistic interactions and impact of alcohol abuse and addiction on the development and progression of HIV-associated neurological disease, applications that propose studies in the context of age-dependent, sex or ethnicity in these special populations are further encouraged. In addition, it is expected that applications will focus on human studies including research involving human postmortem brain tissue, or will employ relevant animal models (simian, feline, rodent) that are readily translatable to the human condition.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information


1. Mechanism of Support

This Funding Opportunity Announcement (FOA) will use the NIH Research Project Grant (R01) award mechanism.  The applicant will be solely responsible for planning, directing, and executing the proposed project.  

This FOA uses “Just-in-Time” information concepts. It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are a U.S. organization and are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 5.4, “Modular Budget Component,” of the Application Guide). 

U.S. applicants requesting more than $250,000 in annual direct costs and all foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096, August 23, 2006.       

At this time, it is not known if competing renewal (formerly “competing continuation”) applications will be accepted and/or if this FOA will be reissued.

2. Funds Available

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 plan of the NIAAA provides support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

The participating organization, NIAAA, intends to commit approximately $1,500,000 dollars in fiscal year 2007 to fund 2 to 3 R01 applications in response to this FOA, plus 5 to 6 R21 applications in response to the parallel FOA [RFA-AA-07-016; Mechanisms of Nervous System Dysfunction: Impact of Alcohol Abuse on HIV-1 Neuropathogenesis (R21)].  

NIH grants policies as described in the NOT-OD-05-004, November 2, 2004.  

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

You may submit an application(s) if your institution/organization has any of the following characteristics:

1.B. Eligible Individuals

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the 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.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a “team science” approach that clearly does not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a single PD/PI or multiple PD/PI grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for multiple PD/PI grants will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PD/PIs will be factored into the assessment of the overall scientific merit of the application.  Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria
 
Applications for renewal or supplementation of existing projects are eligible to compete with applications for new awards. 

Applicants may submit more than one application, provided each application is scientifically distinct.

Section IV. Application and Submission Information


To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/applicants/apply_for_grants.jsp and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

PDs/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.

Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Registered

2) Organizational/Institutional Registration in the eRA Commons

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

Both the PD/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo: Telephone 301-435-0714, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

The SF424 (R&R) application has several components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY includes all applicable components, required and optional. A completed application in response to this FOA includes the data in the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget or Research & Related Budget, as appropriate (See Section IV.6., “Special Instructions,” regarding appropriate required budget component.)
Research & Related Budget (required for foreign applications)

Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

Foreign Organizations (Non-domestic (non-U.S.) Entity)

NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600260.

Applications from foreign organizations must:

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS   

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact” PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of “PD/PI.” Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the “Credential” field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership of the project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” (Section 14 of the Research Plan Component in the SF424 (R&R)), must be included. A rationale for choosing a multiple PD/PI approach should be described.  The governance and organizational structure of the leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators. 

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan.  In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions 

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form. 

When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only. Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using the Modular budget format. See Section 5.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.

3. Submission Dates and Times

See Section IV.3.A. for details.

3.A. Submission, Review, and Anticipated Start Dates
Opening Date: April 14, 2007 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date: April 14, 2007
Application Submission/Receipt Date: May 11, 2007
AIDS Application Submission/Receipt Date: May 11, 2007
Peer Review Date: July/August 2007
Council Review Date: October 2007
Earliest Anticipated Start Date: September 15, 2007

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

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.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Abraham Bautista, Ph.D.
Chief, Extramural Project Review Branch, Office of Extramural Activities
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane,  Room 3039
Bethesda, MD 20892-9304
Telephone: (301) 443-9737
Fax: (301) 443-6077
Email: bautista@mail.nih.gov

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/applicants/apply_for_grants.jsp  and follow steps 1-4. Note:  Applications must only be submitted electronically.  PAPER APPLICATIONS WILL NOT BE ACCEPTED. 

In order to expedite the review, applicants are requested to notify the NIAAA Referral Office by email (bautista@mail.nih.gov) when the application has been submitted.  Please include the FOA number and title, PD/PI name, and title of the application.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission/receipt date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image.

Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the NIAAA. Incomplete and non-responsive applications will not be reviewed. If the application is not responsive to the RFA, NIH staff may contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next appropriate NIH review cycle.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR receives the Grants.gov acknowledgments. The AOR and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific Review Group is also in the Commons. 

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on their application status in the Commons.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an “Introduction” describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

4. Intergovernmental Review

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. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing renewal (formerly “competing continuation”) award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing renewal award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See the
NIH Grants Policy Statement.

6. Other Submission Requirements

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD/PI(s) to fill in his/her Commons User ID in the “PROFILE – Project Director/Principal Investigator” section, “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

PHS398 Research Plan Component Sections

Items 2-5 of the PHS398 Research Plan component are limited to 25 pages. While each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.   

All application instructions outlined in the SF424 (R&R) Application Guide are to be followed, incorporating "Just-in-Time" information concepts, and with the following additional requirements:

Special Instructions for Modular Grant applications

R01 applications from U.S. institutions/organizations requesting up to $250,000 per year in direct costs (excluding consortium F&A costs) must be submitted in a modular budget format. Additional information on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm. When submitting a modular budget, the applicant organization will include only the PHS398 Modular Budget component. See Section 5.4 of the SF424 (R&R) Application Guide for further instructions regarding the use of the PHS398 Modular Budget component.

Foreign organizations may not submit modular budgets. See NOT-OD-06-096

Appendix Materials

IMPORTANT NOTE: NIH has published new limitations on grant application appendix materials to encourage applications to be as concise as possible while containing the information needed for expert scientific review. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html.

Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Note: While each section of the PHS398 Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to monitor better formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

Foreign Applications (Non-domestic (non-U.S.) Entity)

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal Web site, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Sharing Research Resources

NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement  http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590). See Section VI.3., “Reporting.”

Section V. Application Review Information


1. Criteria 

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications submitted for this funding opportunity will be assigned to the NIAAA on the basis of established PHS referral guidelines.

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIAAA in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application.

Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? For applications designating multiple PDs/PIs, is the leadership approach, including the designated roles and responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PDs/PIs?

Innovation:  Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?   

Investigators: Are the PD/PI(s) and other key personnel appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the PD/PI(s) and investigative team bring complementary and integrated expertise to the project (if applicable)? 

Environment:  Do(es) the scientific environment(s) in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?  

2.A. Additional Review Criteria

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed.  See the “Human Subjects Sections” of the PHS398 Research Plan component of the SF424 (R&R)..

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated. See the “Human Subjects Sections” of the PHS398 Research Plan component of the SF424 (R&R)
 
Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the adequacy of the plans for their care and use will be assessed. See the “Other Research Plan Sections” of the PHS398 Research Plan component of the SF424 (R&R).  

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget and Period of Support: The reasonableness of the proposed budget and the appropriateness of the requested period of support in relation to the proposed research may be assessed by the reviewers. The priority score should not be affected by the evaluation of the budget.

Applications from Foreign Organizations: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed. 

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

2.D. Sharing Research Resources

NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement  http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590), See Section VI.3., “Reporting.”
 
Model Organism Sharing Plan: Reviewers are asked to assess the sharing plan in an administrative note. The sharing plan itself should be discussed after the application is scored. Whether a sharing plan is reasonable can be determined by the reviewers on a case-by-case basis, taking into consideration the organism, the timeline, the applicant's decision to distribute the resource or deposit it in a repository, and other relevant considerations.

3. Anticipated Announcement and Award Dates

Not Applicable.

Section VI. Award Administration Information


1. Award Notices

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 NIH eRA Commons

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

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. See Section IV.5., “Funding Restrictions.”       

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.

3. Reporting

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

Section VII. Agency Contacts


We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contact(s):

Roger G. Sorensen, Ph.D., M.P.A.
Division of Neuroscience and Behavior
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 2053
Bethesda, MD 20892-9304
Telephone: (301) 443-2678
Fax: (301) 443-1650
Email: rsorense@mail.nih.gov

2. Peer Review Contact(s):

Abraham Bautista, Ph.D.
Chief, Extramural Project Review Branch, Office of Extramural Activities
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3039
Bethesda, MD 20892-9304
Telephone: (301) 443-9737
Fax: (301) 443-6077
Email: bautista@mail.nih.gov

3. Financial/Grants Management Contact(s):

Judy Fox
Chief, Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3023
Bethesda, MD 20892-9304
Telephone: (301) 443-4704
Fax: (301) 443-3891
Email: jfox@mail.nih.gov

Section VIII. Other Information


Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (“NIH Policy for Data and Safety Monitoring,” NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research” (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov/). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov/) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process, please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov// and view the Policy or other Resources and Tools, including the Authors' Manual.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (HHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles. Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. 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. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy


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