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:  Alcohol, Puberty, and Adolescent Brain Development (R21)

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-07-008

Catalog of Federal Domestic Assistance Number(s)
93.273

Key Dates
Release/Posted Date:  January 4, 2007
Opening Date:  February 16, 2007(Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): March 16, 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 Receipt Date(s):  April 16, 2007
Peer Review Date(s): June/July 2007   
Council Review Date(s): August, 2007
Earliest Anticipated Start Date(s): September 15, 2007
Expiration Date: April 17, 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
    A. Cooperative Agreement Terms and Conditions of Award
3. Reporting

Section VII. Agency Contact(s)
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

PURPOSE

The purpose of this FOA is to support studies on the effects of child and adolescent alcohol use on the developing brain using animal research paradigms.  In humans, the brain continues to develop throughout adolescence and into a person’s early twenties coincident with dramatic hormonal, physiological, and behavioral changes.   In addition, adolescence is a period of changing social contexts, particularly increased relations with peers, when most people initiate and escalate their consumption of alcohol.  During puberty, sex differences in drinking patterns become apparent, and early puberty may create risks for alcohol problems that are sex-dependent.  This initiative offers opportunities to increase our understanding of 1) the degree to which hormonal changes at puberty interact with neurodevelopmental processes to promote sex effects in alcohol use and misuse, and 2) the effects of adolescent alcohol exposure on these interactive processes.  Research is encouraged using a variety of cellular, molecular, neuropharmacological, and physiological tools. Preclinical models are needed to investigate the role of hormones in regulating adolescent brain function and its relation to sex differences in drinking behavior and other actions of alcohol.

BACKGROUND

Adolescence is the period of life during which most youth initiate and escalate alcohol use.  In fact, alcohol is the most commonly abused substance among adolescents. According to the 2005 Monitoring the Future Study, 41.0 percent of 8th graders, 63.2 percent of 10th graders, and 75.1 percent of 12th graders have used alcohol in their lifetime. Of greater concern is the widespread occurrence of heavy episodic drinking defined as drinking five or more drinks in a row during the past two weeks.  For example, according to the 2005 Monitoring the Future Study, the prevalence of this behavior among high school seniors is 28.1 percent. 

Interestingly between the ages of 12 and 17, adolescent males and females have similar patterns of alcohol use and similar prevalence of alcohol abuse and dependence.  By late puberty, however, sex specific patterns begin to emerge, with females exhibiting fewer drinking days in the past month, fewer episodes of heavy drinking, and lower prevalence of alcohol abuse and dependence relative to males. Substantial changes in brain biology, physiology, and architecture occur during the transitions from pre-adolescence through adolescence and into young adulthood.  The hormonal changes of puberty also affect the developing brain and may help explain the disparate drinking trajectories of boys and girls.  Recent evidence suggests that an increase in gonadal steroids and stress response hormones during puberty may influence the structural and functional remodeling of the brain (Andersen, 2003; Sisk and Zehr, 2005). Thus, hormonal mechanisms, such as activation of reproductive hormones, stress responses, and their effects on brain developmental processes could explain the observed sex differences in alcohol drinking patterns during puberty.

With brain development and puberty proceeding at the same time as rapid escalation in alcohol use, it is important to consider potential effects of alcohol on the interaction between pubertal hormone changes and adolescent neurodevelopmental processes and the implications of alcohol-induced changes in these processes on sex differences in future alcohol use and misuse.

Sex Differences in Adolescent Brain Development

Longitudinal data from structural imaging studies show that cortical gray matter development in humans can be depicted an inverted U shape, first increasing and then decreasing.  Regions of the cortex develop at different rates, with the sensory and motor systems maturing earliest and the prefrontal cortex, a region that is part of the reward circuit, developing last. (see for example, Giedd, et al., 1999). Girls attain peak gray matter volume about one year earlier than males, although the rates of these changes are regionally specific However, males overall have an 8-9% larger total cerebral volume than females.  Increases in limbic structures associated with emotional regulation and the alcohol reward system, proceed during adolescence in a sex-dependent manner. Of particular interest is that a sex difference in volume of the bed nucleus of the stria terminalis (a component of the extended amygdala), which is greater in males than females, does not emerge until adolescence.  White matter also increases through adolescence in a linear, but sex-specific pattern.

Evidence from nonhuman primate and rodent studies indicates that unique neuroanatomical and neurochemical changes underlie the gross morphological changes in gray matter volume that are observed during adolescence.  During adolescence there is a significant overproliferation of synapses and receptors in most brain regions, including prefrontal cortex, followed by preferential synaptic elimination (see Spear, 2000; Andersen, 2003 for review). For example, at the same time that loss of excitatory input to the prefrontal cortex is occurring, dopaminergic and cholinergic inputs to the prefrontal cortex increase during adolescence relative to other developmental stages.  Sex and region specific maturational changes occur in volume, synaptic density, types of synapses, and neurotransmitter markers in subcortical structures related to reward circuitry (striatum, accumbens, hippocampus, amygdala, locus coeruleus) during adolescence (Spear, 2000, Sisk and Zehr, 2005 for review).

Alcohol Effects on the Developing Brain – Basic Findings from Animal Studies

Electrophysiological and behavioral studies suggest that adolescence is a period of heightened vulnerability to the deleterious effect of alcohol on the brain, particularly the hippocampus, a key region for encoding new information.  Ethanol-induced inhibition of N-methyl-D-aspartate (NMDA) mediated synaptic potentials and long-term potentiation in rat hippocampal slices is greater in adolescents than adults (White and Swartzwelder, 2005).  In addition, chronic alcohol exposure during adolescence, but not adulthood, increases cortical NMDA receptor levels and produces long-lasting changes in hippocampal neurophysiological responses and spatial learning (Slawecki, et al., 2001; Sircar and Sircar 2006).  High-dose, four-day binge alcohol exposure in adolescent or adult rats results in brain damage in both age groups, but only the adolescent exposed animals manifest damage in the frontal cortical olfactory regions, the entorhinal cortex, and the anterior portions of the piriform and perirhinal cortices. Finally, acute high doses of ethanol inhibit adolescent neurogenesis of neural progenitor cells, a marker of neuronal growth, in the rat hippocampus and forebrain (Crews, et al., 2000, 2006). Taken together, these few studies indicate that the adolescent brain is more susceptible to overt damage and disruption of cellular, physiological, neurochemical, and behavioral processes by acute and chronic doses of alcohol.  However, more research is needed on hormonal regulation of neurodevelopmental processes and neural circuit development, and their relationship to sex differences in long-term behavioral consequences, including drinking behavior.

Interactions between Alcohol Drinking, Pubertal Hormones, and Adolescent Brain Development

The sexual dimorphisms in brain structure and function during adolescence are traditionally thought to result from organizational effects of gonadal steroid hormones on the central nervous system during critical periods of perinatal development.  More recently, however, it has been suggested that the adolescent phase of neural remodeling may be another period of steroid-dependent refinement of neural circuits that results in relatively long-lasting effects on adult behavior, including those that affect risk for alcoholism (Sisk and Zehr, 2005).  There is now substantial evidence that steroid receptors are widely distributed throughout the brain and influence neurodevelopment and behavior.  Furthermore, manifestation of sex differences in the neuroanatomy or neurochemistry of certain brain regions, but not others, are influenced by pubertal gonadal hormones (Andersen, et al., 2002; Sisk and Zehr, 2005).  Differences in stress responsiveness and exposure to stress hormones at different postnatal stages may also affect sex differences in neuroanatomical, physiological, and behavioral development (see Andersen, 2003). 

Despite the renewed interest in the potential role of elevated hormone levels during puberty on remodeling the adolescent brain, the impact of interactions between pubertal hormone changes and basic neurodevelopmental processes on sex differences in drinking behavior has received little attention. Evidence in adult humans and animals indicates that gonadal hormones, neurosteroids, and stress hormones influence alcohol consumption and or alcohol actions in a sex-specific manner.  However, very few studies have investigated the developmental progression of these sex differences in alcohol drinking and/or the influence of pubertal hormones on this process (Witt, in press, Neurotoxicology and Teratology).  For example, only one study in rats has focused on the emergence of sex-specific drinking patterns in the early post pubertal period (Lancaster, et al., 1996).  Female rats show a greater stress response to acute alcohol administration, with sex differences emerging prepubertally (postnatal days 21-26), but not reaching adult levels until adulthood (Ogilvie and Rivier, 1996; Silveri and Spear, 2004). Hormone replacement studies in neonatal and adult rats suggest that activation of pubertal gonadal steroids are responsible for the emergence of these sex differences in alcohol drinking and actions during adolescence, but there are no studies that examine the effects of the presence or absence gonadal steroids at puberty on these behaviors. Adolescence is a time when both males and females are becoming initiated to alcohol and some begin drinking heavily.  Thus, it is important that we begin to understand the neuropharmacological, cellular, and molecular mechanisms by which changes in various hormone systems at puberty may modify reward circuitry during adolescence to promote sex differences in drinking behavior as well as on the actions of adolescent alcohol exposure in shaping hormonal, brain, and behavioral development.

ADDITIONAL INFORMATION

Examples of research areas of interest to NIAAA include the following:

This FOA is intended to publicize NIAAA’s interest in establishing models to study alcohol’s effects the interaction of pubertal hormones and adolescent brain changes in causing excessive adolescent drinking in laboratory animal paradigms.  Investigators wishing to obtain support for such research who lack expertise in alcohol research should seek collaboration with investigators experienced in alcohol research, insofar as such experience will prove essential for proper study design and data analysis.  Investigators desiring to establish such collaborations are encouraged to contact the individual mentioned under Scientific/Research Contacts below.

REFERENCES

Andersen SL, Thompson AP, Krenzel, E, Teicher MH. (2002) Pubertal changes in gonadal hormones do not underlie adolescent dopamine receptor overproduction.  Psycholneuroendocrinol, 27:683-691.

Andersen SL. (2003). Trajectories of brain development:  Point of vulnerability or window of opportunity?  Neurosci Biobehav Rev, 27:3-18.

Crews FT, Braun, CJ, Hoplight B, Switzer RC III., & Knapp DJ (2000). Binge ethanol  consumption causes differential brain damage in young adolescent rats compared with adult rats. Alc Clin Experimental Res 24:1712-1723.

Crews FT, Mdzinarishvili A, Kim D, He J, Nixon K. (2006) Neurogenesis in adolescent brain is potently inhibited by ethanol.  Neuroscience, 137:437-435.

Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, Paus T, Evans AC, Rapoport JL.  (1999). Brain development during childhood and adolescence:  a longitudinal MRI study.  Nat Neurosci, 2:861-863.

Lancaster FE, Brown TD, Coker KL, Elliott JA, Wren SB. (1996). Sex differences in alcohol preference and drinking patterns emerge during the early postpubertal period in Sprague-Dawley rats.  Alc Clin Exp Res, 20:1043-1049.

Ogilvie KM, Rivier C. (1996). Gender differences in alcohol-evoked hypothalamic-pituitary adrenal activity in the rat:  ontogeny and role of neonatal steroids.  Alcohol  Clin Exp Res, 20:255-261.

Silveri MM, Spear LP. (2004). Characterizing the ontogeny of ethanol-associated increases in corticosterone.  Alcohol, 32:145-155.

Sircar R, Sircar D. (2006) Repeated alcohol treatment in adolescent rats alters cortical NMDA receptor.  Alcohol, 39:51-58.

Sisk CL, Zehr JL. (2005). Pubertal hormones organize the adolescent brain and behavior.  Front Neuroendocrinol, 26:163-174.

Slawecki CJ, Betancourt M, Cole M, Ehlers CL. (2001) Periadolescent alcohol exposure has lasting effects on adult neurophysiological function in rats.  Dev Brain Res, 128:63-72.

Spear LP.  (2000). The adolescent brain and age-related behavioral manifestations.  Neurosci Biobehav Rev, 24:417-463.

White AM, Swartzwelder S. (2005) Age-related effects of alcohol on memory and memory-related brain function in adolescents and adults.  Recent Dev Alcohol, 17:161-176

Witt, ED (in press) Puberty, hormones, and sex differences in alcohol abuse and dependence.  Neurotoxicology and Teratology.

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 Exploratory/Development (R21) grant 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 budget formats (see the “Modular Applications and Awards” section of the NIH Grants Policy Statement. Specifically, if you 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).

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.

The Exploratory/Developmental mechanism (R21) will not allow a renewal (competing continuation).

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 plans of the Institutes and Centers (ICs) provide 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 total project period for an application submitted in response to this funding opportunity may not exceed 2 years. Although the size of award may vary with the scope of research proposed, it is expected that applications will stay within the budgetary guidelines for an exploratory/developmental project. Direct costs are limited to $275,000 over a two-year period, with no more than $200,000 in direct costs allowed in any single year. Applicants may request direct costs in $25,000 modules, up to the total direct costs limitation of $275,000 for the combined two-year award period.

The participating organization(s) National Institute on Alcohol Abuse and Alcoholism intends to commit approximately $1.0 million dollars in FY2007 to fund approximately 1-4 applications.

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.

Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation. See 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 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.

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

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/Apply/ 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 Started

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 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 is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY will include all applicable components, required and optional. A completed application in response to this FOA will include 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
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/grants/policy/nihgps_2003/NIHGPS_Part12.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.

component.

3. Submission Dates and Times

See Section IV.3.A for details.

3.A. Submission, Review, and Anticipated Start Dates

Opening Date:  February 16, 2007(Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): March 16, 2007
Application Receipt Date(s): April 16, 2007
Peer Review Date(s): June/July 2007
Council Review Date(s): August, 2007
Earliest Anticipated Start Date(s): 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 P. Bautista, Ph.D.
Chief, Extramural Project Review Branch
Office of Extramural Activities
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Ln Room 3039
Rockville, MD 20852
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/Apply 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 Center for Scientific Review, NIH. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. 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. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/nihgps_2003/index.htm

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 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 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.

http://grants.nih.gov/grants/policy/nihgps_2003/index.htm

6. Other Submission Requirements

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

The NIH requires the PD/PI 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. 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 “Registration FAQs – Important Tips -- Electronic Submission of Grant Applications.”

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.”

Warning: Please be sure that you observe the direct cost, project period, and page number limitations specified above for this FOA. Application processing may be delayed or the application may be rejected if it does not comply with these requirements.

Research Plan Component Sections

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 requirements for R21 applications:

Appendix Materials

The following materials may be included in the Appendix:

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

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

Plan for Sharing Research Data

Not Applicable

Sharing Research Resources

Not Applicable

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 ICs on the basis of established Public Health Service (PHS) referral guidelines.

Appropriate scientific review groups convened in accordance with the standard NIH peer review procedures (http://cms.csr.nih.gov/ResourcesforApplicants/) will evaluate applications for scientific and technical merit.

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, does the Leadership Plan ensure that there will be sufficient coordination and communication among the PDs/PIs?  Are the administrative plans for the management of the research project appropriate, including plans for resolving conflicts? 

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 investigators 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 investigative team bring complementary and integrated expertise to the project (if applicable)?

Environment: Does the scientific environment 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:

Resubmission Applications (formerly “revised/amended” applications): Are the responses to comments from the previous scientific review group adequate? Are the improvements in the resubmission application appropriate?

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 item 6 of the Research Plan component of the SF424 (R&R).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from 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 item 7 of the 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 five items described under item 11 of the Research Plan component of the SF424 (R&R) will be assessed.

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: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. 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

Not Applicable

2.D. Sharing Research Resources

Not Applicable

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/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 Contacts:

Ellen D. Witt, Ph.D.
Division of Neuroscience and Behavior
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane
Room 2055, MSC 9304
Bethesda, MD 20892-9304
Tel:  301-443-6545
Fax:  301-443-1650
Email:  ewitt@mail.nih.gov

2. Peer Review Contacts:

Abraham P. Bautista, Ph.D.
Chief, Extramural Project Review Branch
Office of Extramural Activities
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Ln Room 3039
Rockville, MD 20852
Telephone: (301) 443-9737
Fax: (301) 443-6077
Email: bautista@mail.nih.gov  

3. Financial or Grants Management Contacts:

Ms. Judy Fox
Chief, Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3023, MSC 9304
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) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

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


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