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 Institutes on Alcohol Abuse and Alcoholism, (http://www.niaaa.nih.gov)

Title: Medications Development for the Treatment of Alcoholism (SBIR [R43/R44])

Announcement Type
This is a reissue of RFA-AA-06-006 which was previously released January 20, 2006

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) SBIR/STTR 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-07-009

Catalog of Federal Domestic Assistance Number(s)
93.273

Key Dates
Release/Posted Date: January 22, 2007
Opening Date:  February 25, 2007 (Earliest date an application may be submitted to grants.gov)
Letters of Intent Receipt Date(s): March 25, 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: April 25, 2007
Peer Review Date(s): June/July 2007
Council Review Date(s): August 2007
Earliest Anticipated Start Date(s): December 2007
Additional Information To Be Available Date (URL Activation Date): Not Applicable
Expiration Date: April 26, 2007

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

Purpose: The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is seeking research grant applications on the development of medications for alcohol abuse/dependence.   Investigations are needed on pharmacological agents that prevent or reduce alcohol intake by, e.g., decreasing alcohol craving/urge to drink and/or alleviating the negative symptoms associated with drinking cessation.

• Funds Available and Anticipated Number of Awards: NIAAA intends to commit up to $2 million for FY2007.  Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications. Approximately 3 to 6 awards will be made in response to this FOA.
• Mechanism of Support: This FOA will utilize the SBIR (R43/R44) grant mechanisms for Phase I, Phase II, Fast-Track and, Phase II Competing Renewal applications and runs in parallel with a FOA of identical scientific scope, RFA-AA-07-010 that solicits applications under the Small Business Technology Transfer (STTR) (R41/R42) grant mechanisms.
• Eligible Institutions/Organizations: Only United States SBCs are eligible to submit SBIR applications. A SBC is one that, on the date of award for both Phase I and Phase II funding agreements, meets ALL of the criteria as described in Section III.  
• Eligible Project Directors/Principal Investigators: Individual with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their 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. On an SBIR application, the Project Director/Principal Investigator (PD/PI) must have his/her primary employment (more than 50%) with the SBC at the time of award and for the duration of the project.
• Number of Applications: Applicant SBCs may submit more than one application, provided each application is scientifically distinct. 
• Resubmissions.  Applicants may submit a resubmission application, but such application must include an Introduction (1 page maximum for Phase I and 3 pages maximum for Phase II) addressing the previous peer review critique (Summary Statement).
• Number of PDs/PIs. More than one PD/PI, or multiple PDs/PIs, may be designated on the application.
• Application Materials: See Section IV.1 for application materials. The SF424 (R&R) SBIR/STTR Application Guide for this FOA is located at these Web sites:
• http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_SBIR_STTR_Ver2.doc  (MS Word)
• http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_SBIR_STTR_Ver2.pdf  (PDF)
• General Information: For general information on SF424 (R&R) Application and Electronic Submission, see these Web sites:
• SF424 (R&R) Application and Electronic Submission Information: http://grants.nih.gov/grants/funding/424/index.htm
• General information on Electronic Submission of Grant Applications: http://era.nih.gov/ElectronicReceipt/
• Hearing Impaired: Telecommunications for the hearing impaired is available at: TTY 301-451-5936.

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 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

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is seeking research grant applications on the development of medications for treatment of alcohol abuse/dependence. Investigations are needed on pharmacological agents that prevent or reduce alcohol intake.

Background

Recent advances in the development of medications to treat alcoholism are highlighted by FDA approval of naltrexone and acamprosate for this indication. (see review by Litten et al, 2005). Advances have also been made in understanding the biological mechanisms underlying alcohol drinking, with recognition that alcohol acts at numerous sites, and many of through many pathways. Many of these provide treatment targets. Naltrexone, for example, is an opiate antagonist and acamprosate apparently acts to stabilize glutamate function in the abstinent alcoholic. Multiple neurotransmitter, neuromodulator, and hormonal systems are involved in problematic drinking. These include opioid, serotonin, dopamine, gamma-aminobutyric acid (GABA), glutamate, neuropeptide Y (NPY), cannabinoid, and hypothalamic-pituitary-adrenal (HPA) systems (Litten et al., 2005) This developing knowledge base has led to identification of many possible biological targets for testing novel pharmacological agents.

Two important clinical trials of naltrexone first demonstrated its efficacy in alcohol dependent patients and contributed significantly to its FDA approval (Volpicelli et al., 1992 and O'Malley et al., 1992). Naltrexone is not a cure for alcoholism, but appears to have a moderate effect in reducing drinking, particularly in reducing relapse to heavy drinking (Anton et al., 1999; Anton et al., 2005; Morris et al., 2001; Heinala et al., 2001). Patient compliance plays a significant role in the efficacy of naltrexone (Volpicelli et al., 1997; Chick et al., 2000; Monti et al., 2001), but even given compliance, naltrexone is not be effective for all alcoholics (Kranzler et al., 2000; Krystal et al, 2001). Several studies are currently being funded to address issues surrounding the clinical use of naltrexone, such treatment duration, optimal dose, identification of patient predictors of favorable treatment outcome, optimal combination with behavioral/psychosocial interventions, and efficacy in combination with other medications.

Acamprosate was studied extensively and approved in Europe years before approval in the US. Studies have consistently shown that individuals treated with acamprosate are more likely to complete treatment, have longer times to their first drink, have greater abstinence rates, and demonstrate longer cumulative abstinence periods than placebo-treated patients (Mason, 2005). Still, acamprosate does not work for everyone (Anton et al., 2006). Acamprosate's mechanism of action has yet to be definitively identified, although several studies suggest that it may modulate activity of the glutamate system (Mason, 2005)

The serotonergic system has also been implicated in drinking. The serotonin 3 (5-HT₃) receptor regulates dopamine release in the mesolimbic area, particularly in the nucleus accumbens. Ondansetron, a 5-HT₃ antagonist, reduces desire to drink in humans and augments stimulant and sedative effects of alcohol (Johnson et al., 1993; Swift et al., 1996). In a 12-week trial, ondansetron reduced frequency and quantity of alcohol consumption in early onset alcoholics, but not in late onset alcoholics. In a preliminary study, combination of ondansetron and naltrexone reduced alcohol craving and improved drinking outcome to a greater extent than had either compound alone (Johnson et al., 2000; Ait-Daoud et al., 2001).

Results of selective serotonin reuptake inhibitors (SSRIs) in human alcohol trials have yielded inconsistent on alcohol drinking measures (Pettinati, 1996, Kranzler, 2000). It has been suggested that subpopulations of alcohol dependent patients respond differently to the SSRIs. For example, Kranzler et al. (1996) and Pettinati et al. (2000) found that higher-risk/severity type B alcoholics had less favorable treatment outcome to SSRIs than lower-risk/severity type A alcoholics. Cornelius et al. (1997) found that fluoxetine reduced depressive symptoms and alcohol intake in severe inpatient populations of alcoholics with major depression and suicide risk. In contrast, Pettinati et al. (2001) and McGrath (1998) reported that fluoxetine and sertraline were no better than placebo in improving depression and reducing drinking in a less severely affected sample of depressed alcoholics.

Because the medications developed to date show, at best, small to medium effect in reducing or preventing drinking, developing and evaluating new, more efficacious medications remains a high priority. Several promising agents could lead to clinical testing. These include, but are not limited to, memantine, a non-competitive NMDA antagonist (Holter et al., 1996); kudzu and its purified active components (e.g., puerarin) (Keung and Vallee, 1993; Lin et al., 1996); corticotropin-releasing factor (CRF) antagonists (Bell et al., 1998; Richter et al., 2000); opioid receptor antagonists such as delta2 antagonist naltriben (June et al., 1999); synthetic neurosteroids (Morrow et al., 1999); FG 5974 (and its analogues) a 5-HT_1A/5HT_2A antagonist (Roberts et al., 1998); agents with selective affinity to GABA_A alpha1 or GABA_A alpha 5 receptor subunits (June et al., 2001, Harvey et al., 2002), mGluR₅ antagonists (Backstrom et al. 2004); mGluR2/3 agonists (Baptista et al., 2004); cannabinoid CB₁ antagonists (Serra et al., 2001; Columbo et al., 2004); NOP agonists (Ciccocioppo et. al, 2004); and NPY Y₂ antagonists (Rimondini et al., 2005)

A spectrum of neurotransmitter systems (e.g., GABA, NMDA, 5-HT, dopamine), neuropeptide systems (neuropeptide Y, leptin), signal transduction pathways (PKA, PKC), and gene transcription factors (delta fosB) have been implicated in alcohol dependence and craving.  New therapeutic compounds may act on known ethanol targets, or may act upon newly identified therapeutic targets not yet examined in relation to alcohol.  As basic research reveals promising targets relevant to alcohol abuse and its consequences, analogs acquired from existing libraries, or newly-synthesized analogs developed through computational and combinatorial chemistry can be screened in vitro or in standardized behavioral assays for potential therapeutic efficacy.

Advances in molecular genetics (e.g., microarray analysis, targeted mutations, and proteomics) offer powerful approaches for identifying molecular participants in the neurobiological processes of adapting to alcohol and adapting to its subsequent absence. Changes in gene expression and protein concentration can be identified in specific brain regions in temporal relation to alcohol exposure.  Such studies may identify biochemical pathways and brain circuits which are preferentially involved in development of alcohol dependence. Receptors or pathways involved in alcohol drinking and other alcohol effects can be blocked selectively with targeted knockout strategies. Targets for modification of the neurological changes underlying craving and alcohol-seeking after periods of prolonged abstinence can be identified.

SPECIFIC AREAS OF INTEREST INCLUDE

NIAAA is committed to the development and assessment of pharmacological agents to treat alcohol use disorders as well as the more prevalent and severe medical conditions associated with chronic drinking. Compounds may be new, off the shelf, or already approved for another medical disorder. Pharmacological agents of interest can be categorized by function as follows:

• Agents to reduce drinking and/or agents to prolong abstinence.
• Agents to decrease craving or urge to drink including drinking maintained through positive and negative reinforcement mechanisms.
• Agents to attenuate the negative hedonic symptoms of chronic drinking, sometimes referred to as protracted abstinence or protracted withdrawal. This includes targeting pathways responsible for stress and anxiety.
• Agents that restore the impaired cognitive function associated with chronic heavy drinking.
• Agents to diminish drinking by alleviating co-occurring psychiatric pathology and other drug use.

REFERENCES

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Anton, R.F., Moak, D.H., Waid, L.R., Latham, P.K., Malcolm, R.J. and Dias, J.K. (1999) Naltrexone and cognitive behavioral therapy for the treatment of outpatient alcoholics: Results of a placebo-controlled trial. Am J Psychiatry 156:1758-1764.

Anton,R, Moak, D, Latham P, Waid R, Myrick., Voronin, Thevos, A, Wang, W, Woolson, R. (2005) Naltrexone  combined with either cognitive behavioral of motivational enhancement therapy for alcohol dependence.  J Clin Psychopharmacol 25:349-357.

Anton R, O Malley SS, Ciraulo DA, et al (2006) Combined pharmacotherapies and behavioral intervetions for alcohol dependence: The COMBINE study. JAMA 295:2003-2017.

Backstrom, P, Bachteler, D., Koch, S, Hyytia,P., Spanagel, R. (2004) mGluR₅  antagonist MPEP reduces ethanol-seeking and relapse behavior. Neuropsychopharmacology 29:921-928.

Baptista MAS, Martin-Fardon R, Weiss F (2001) Preferential effects of metaboltropic glutamate 2/3 receptor agonist LY379268 on conditioned reinstatement versus primary reinforcement: Comparison between cocaine and a potent conventional reinforcer. J Neurosci 24:4723-4727.

Bell, S.M., Reynolds, J.G., Thiele, T.E., Gan, J., Figlewicz, D.P., and Woods, S.C. (1998) Effects of third intracerebroventricular injections of corticotropin-releasing factor (CRF) on ethanol drinking and food intake. Psychopharmacology 139:128-135.

Chick, J., Anton, R., Checinski, K., Croop, R., Drummond, D.C., Farmer, R., Labriola, D., Marshall, J., Moncrieff, J., Morgan, M.Y., Peters, T., and Ritson, B. (2000) A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse. Alcohol Alcohol 35:587-593.

Ciccocioppo R, Economidou D, Fedeli A et al. (2004) Attenuation of ethanol self-administration and of conditioned reinstatement of alcohol-seeking behaviour by the antiopioid peptide nociceptin/orphanin FZ in alcohol-preferring rats. Psychopharmacologyl 172:170-178.

Columbo, G., Vacca, G., Serra., Carai, M., Gessa, G. (2004) Supressing effect of the cannabinoid CB₁ receptor antagonist, SR 141716, on alcohol’s motivational properties in alcohol-preferring rats.  Eur J. Pharmacol 498:119-123.

Cornelius, J.R., Salloum, I.M., Ehler, J.G., Jarrett, P.J., Cornelius, M.D., Perel, J.M., Thase, M.E., and Black, A. (1997) Fluoxetine in depressed alcoholics: A double-blind, placebo-controlled trial. Arch Gen Psychiatry 54:700-705.

Harvey, S.C., Foster, K.L., McKay, P.F., Carroll, M.R., Seyoum, R., Woods J.E., Grey, C., Jones, C.M., McCane, S., Cummings, R., Mason, D., Ma, C., Cook, J.M., and June, H.L.  (2002).  The GABA(A) receptor alpha1 subtype in the ventral pallidum regulates alcohol seeking behaviors.  JNeurosci  22:3765-75.

Heinala, P., Alho, J., Kiianmaa, K., Lonnqvist, J., Kuoppasalmi, K., and Sinclair, J.D. (2001) Targeted use of naltrexone without prior detoxification in the treatment of alcohol dependence: A factorial double-blind, placebo- controlled trial. J Clin Psychopharmacol 21:287-292.

Holter, S.M., Danysz, W., and Spanagel, R. (1996) Evidence for alcohol anti- craving properties of memantine. Eur J Pharmacol 314:R1-R2.

Johnson, B.A., Campling, G.M., Griffiths, P., and Cowen, P.J. (1993) Attenuation of some alcohol-induced mood changes and the desire to drink by 5- HT3 receptor blockade: A preliminary study in healthy male volunteers. Psychopharmacology 112:142-144.

Johnson, B.A., Ait-Daoud, N., and Prihoda, T.J. (2000) Combining ondansetron and naltrexone effectively treats biologically predisposed alcoholics: From hypotheses to preliminary clinical evidence. Alcohol Clin Exp Res 24:737-742.

June, H.L., Harvey, S.C., Foster, K.L., McKay, P.F., Cummings, R., Garcia, M., Mason, D., Grey, C., McCane, S., Williams, L.S., Johnson, T.B., He, X., Rock, S., and Cook, J.M. (2001)  GABA(A) receptors containing (alpha)5 subunits in the CA1 and CA3 hippocampal fields regulate ethanol-motivated behaviors: An extended ethanol reward circuitry. Journal of Neurosci 21:2166-77.

June, H.L., McCane, S.R., Zink, R.W., Portoghese, P.S., Li, T.K., and Froehlich, J.C. (1999) The d2-opioid receptor antagonist naltriben reduces motivated responding for ethanol. Psychopharmacology 147:81-89.

Keung, W-M., and Vallee, B.L. (1993) Daidzin and daidzein suppress free-choice ethanol intake by Syrian Golden hamsters. Proc Natl Acad Sci 90:10008-10012.

Kranzler, H.R., Burleson, J.A., Brown, J., and Babor, T.F. (1996) Fluxoxetine treatment seems to reduce the beneficial effects of cognitive-behavioral therapy in type B alcoholics. Alcohol ClinExpRes20:1534-1541.

Kranzler, H.R., Modesto-Lowe, V., and Van Kirk, J. (2000) Naltrexone vs. nefazodone for treatment of alcohol dependence: A placebo-controlled trial. Neuropsychopharmacology 22:493-503.

Krystal, J.H., Cramer, J.A., Krol, W.F., Kirk, G.F., and Rosenheck, R.A. (2001) Naltrexone in the treatment of alcohol dependence. The New Eng J Med 345:1734-1739.

Lin, R.C., Guthrie, S., Xie, C-Y., Mai, K., Lee, D.Y., Lumeng, L., and Li, T- K. (1996) Isoflavonoid compounds extracted from Pueraria labata suppress alcohol preference in a pharmacogenetic rat model of alcoholism. Alcohol Clin Exp Res Litten 20:659-663.

Litten, R. Z., Fertig, J., Mattson, M. and Egli, M. (2005) Development of medications for alcohol use disorders: recent advances and ongoing challenges. Expert Opin Emerging Drugs 10(2): 323-343.

Mason, B. J. (2005) Acamprosate in the treatment of alcohol dependence. Expert OpinPharmacotherapy 6(12): 2103-2105.

McGrath, P.J. (1998) Antidepressant treatment outcomes for primary depression comorbid with alcoholism. Presented at the Scientific Meeting of the Research Society on Alcoholism, Hilton Head Island, South Carolina.

Monti, P.M., Rohsenow, D.J., Swift, R.M., Gulliver, S.B., Colby, S.M., Mueller, T.I., Brown, R.A., Gordon, A., Abrams, D.B., Niaura, R.S., and Asher, M.K. (2001) Naltrexone and cue exposure with coping communication skills training for alcoholics: Treatment Process and 1-year outcomes. Alcohol Clin Exp Res 25:1634-1647.

Morris, P.LP., Hopwood, M., Whelan, G., Gardiner, J., and Drummond, E. (2001) Naltrexone for alcohol dependence: A randomized controlled trial. Addiction 96:1565-1573. 

Morrow, A.L., Janis, G.C., VanDoren, M.J., Matthews, D.B., Samson, H.H., Janak, P.H., and Grant, K.A. (1999) Neurosteroids mediate pharmacological effects of ethanol: A new mechanism of ethanol action? Alcohol Clin Exp Res 23:1933-1940.

O'Malley, S.S., Jaffe, A.J., Chang, G., Schottenfeld, R.S., Meyer, R.E. and Rounsaville, B. (1992) Naltrexone and coping skills therapy for alcohol dependence: A controlled study. Arch Gen Psychiatry 49:881-887.

Pettinati, H.M. (1996) Use of serotonin selective pharmacotherapy in the treatment of alcohol dependence. Alcohol Clin Exp Res 20:23A-29A.

Pettinati, H.M., Volpicelli, J.R., Kranzler, H.R., Luck, G., Rukstalis, M.R. and Cnaan, A. (2000) Sertraline treatment for alcohol dependence: Interactive effects of medication and alcoholic subtype. Alcoholism: Clin Exp Res 24:1041-1049.

Pettinati, H.M., Volpicelli, J.R., Luck, G., Kranzler, H.R., Rukstalis, M.R. and Cnaan, A. (2001) Double-blind clinical trial of sertraline treatment for alcohol dependence. J Clin Psychopharmacology 21:143-153.

Richter, R.M., Zorrilla, E.P., Basso, A.M., Koob, G.F., and Weiss, F. (2000) Altered amygdalar CRF release and increased anxiety-like behavior in sardinian alcohol-preferring rats: A microdialysis and behavioral study. Alcohol Clin Exp Res 24:1765-1772.

Rimondini R, Thorsell A, Heilig M (2005) Suppression of ethanol self-administration by the neuropeptide Y (NPY) Y 2 receptor antagonist BIIE0246: Evidence for sensitization in rats with a history of dependence. Neurosci Lett 375:129-133.

Roberts, A.J., McArthur, R.A., Hull, E.E., Post, C. and Koob, G.F. (1998) Effects of amperozide, 8-OH-DPAT, and FG 5974 on operant responding for ethanol. Psychopharmacology 137:25-32.

Serra, S., Carai, M, Brunetti, G., et al,. (2001) The cannaboid receptor antagonist SR 141716 prevents acquisition of drinking behavior in alcohol-preferring rats.  Eur. J. Pharmacol 430:369-371.

Swift, R.M., Davidson, D., Whelihan, W., and Kuznetsov O. (1996) Ondansetron alters human alcohol intoxication. Biol Psychiatry 40:514-521.

Volpicelli, J.R., Alterman, A.I., Hayashida, M. and O'Brien, C.P. (1992) Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 49:876-880.

Volpicelli, J.R., Rhines, K.C., Rhines, J.S. Volpicelli, J.A., Alterman, A.I and O'Brien, C.P. (1997) Naltrexone and alcohol dependence. Arch Gen Psychiatry 54:737-742.

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

Section II. Award Information

1. Mechanism(s) of Support

This funding opportunity will use the Small Business Innovation Research (SBIR [R43/R44] grant mechanisms. Applications may be submitted for support as Phase I, Phase II, or Fast-Track grants as described in the SF424 (R&R) SBIR/STTR Application Guide. Applications for Phase II Competing Renewal grants may be submitted.

Small business concerns that have received a Phase I SBIR grant may apply for Phase II funding of that project. The Phase II must be a logical extension of the Phase I research but not necessarily as a Phase I project supported in response to this funding opportunity. Phase II applications will compete with all SBIR applications and will be reviewed according to the customary peer review procedures.

The applicant small business concern (SBC) will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses Just-in-Time information concepts. The modular budget format is not accepted for SBIR grant applications. Applicants must complete and submit budget requests using the SF424 Research and Related (R&R) Budget component found in the application package attached to this FOA in Grants.gov/Apply. All other participating organizations, including the partnering research institution, must complete and submit requests using the Research & Related Subaward Budget Attachment(s) Form contained in the application package.

2. Funds Available

The SF424 (R&R) SBIR/STTR Application Guide indicates the statutory guidelines of funding support and project duration periods for Phase I and Phase II SBIR awards. For this funding opportunity, budgets up to $200,000  total costs per year and time periods up to 2 years for Phase I may be requested.  Budgets up to $500,000 total costs per year for up to 2 years  may be requested for Phase II.  Phase II Competing Renewal requests should not exceed $750,000  total costs per year for up to three years. Total costs include direct costs, F&A, and fee/profit.

NIAAA intends to commit up to two (2) million dollars in FY07 to fund 3-6 Phase I and/or Phase II, or Phase II Competing Renewal applications under the SBIR set-aside funding mechanism. Although the financial plans of the participating organizations provide support for this program, awards pursuant to this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

Only United States small business concerns (SBCs) are eligible to submit SBIR applications. A small business concern is one that, at the time of award for both Phase I and Phase II SBIR awards, meets all of the following criteria:

1. Is independently owned and operated, is not dominant in the field of operation in which it is proposing, has a place of business in the United States and operates primarily within the United States or makes a significant contribution to the US economy, and is organized for profit.

2. Is (a) at least 51% owned and controlled by one or more individuals who are citizens of, or permanent resident aliens in, the United States, or (b) for SBIR only, it must be a for-profit business concern that is at least 51% owned and controlled by another for-profit business concern that is at least 51% owned and controlled by one or more individuals who are citizens of, or permanent resident aliens in, the United States.

3. Has, including its affiliates, an average number of employees for the preceding 12 months not exceeding 500, and meets the other regulatory requirements found in Title 13 Code of Federal Regulations (CFR) Part 121. Business concerns are generally considered to be affiliates of one another when either directly or indirectly, (a) one concern controls or has the power to control the other; or (b) a third-party/parties controls or has the power to control both.

Control can be exercised through common ownership, common management, and contractual relationships. The term "affiliates" is defined in greater detail in 13 CFR 121.103. The term "number of employees" is defined in 13 CFR 121.106.

A business concern may be in the form of an individual proprietorship, partnership, limited liability company, corporation, joint venture, association, trust, or cooperative. Further information may be obtained at http://sba.gov/size, or by contacting the Small Business Administration's (SBA) Government Contracting Area Office or Office of Size Standards.

One of the circumstances that would lead to a finding that an organization is controlling or has the power to control another organization involves sharing common office space and/or employees and/or other facilities (e.g., laboratory space). Access to special facilities or equipment in another organization is permitted (as in cases where the awardee organization has entered into a subcontractual agreement with another organization for a specific, limited portion of the research project). However, research space occupied by an SBIR awardee organization must be space that is available to and under the control of the SBIR awardee for the conduct of its portion of the proposed project.

Title 13 CFR 121.3 also states that control or the power to control exists when key employees of one concern organize a new concern ... and serve as its officers, directors, principal stockholders, and/or key employees, and one concern is furnishing or will furnish the other concern with subcontracts, financial or technical assistance, and/or other facilities, whether for a fee or otherwise. Where there is indication of sharing of common employees, a determination will be made on a case-by-case basis of whether such sharing constitutes control or the power to control.

For purposes of the SBIR program, personnel obtained through a Professional Employer Organization or other similar personnel leasing company may be considered employees of the awardee. This is consistent with SBA’s size regulations, 13 CFR 121.106 Small Business Size Regulations.

All SBIR grant applications will be examined with the above eligibility considerations in mind. If it appears that an applicant organization does not meet the eligibility requirements, NIH will request a size determination by the SBA. If eligibility is unclear, NIH will not make an SBIR award until the SBA provides a determination.

Note: An applicant organization that has been determined previously by SBA to be other than small for a size standard of not more than 500 employees or for purposes of the SBIR/STTR program, the organization must be recertified by the SBA prior to any future SBIR/STTR awards.

1.B. Eligible Individuals

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

Under the SBIR program, for both Phase I and Phase II, the primary employment of the PD/PI must be with the small business concern at the time of award and during the conduct of the proposed project. For projects with multiple PD/PIs, at least one must meet the primary employment requirement and will be referred to as the small business PD/PI. Primary employment means that more than one half of the PD/PI’s time is spent in the employ of the small business concern. Primary employment with a small business concern precludes full-time employment at another organization. Occasionally, deviations from this requirement may occur. Such deviations must be approved in writing by the grants management officer after consultation with the NIH SBIR/STTR Program Coordinator.

If the application has the likelihood for funding, the awarding component will require documentation to verify the eligibility of the small business PD/PI, if at the time of submission of the application, the small business PD/PI is a less-than-full-time employee of the small business concern, is concurrently employed by another organization, or gives the appearance of being concurrently employed by another organization, whether for a paid or unpaid position.

If the PD/PI is employed or appears to be employed by an organization other than the applicant organization in a capacity such as Research Fellow, Consultant, Adjunct Professor, Clinical Professor, Clinical Research Professor, or Associate, a letter must be provided by each employing organization confirming that, if an SBIR grant is awarded to the applicant small business concern, the small business PD/PI is or will become a less-than-half-time employee of such organization and will remain so for the duration of the SBIR project. If the small business PD/PI is employed by a university, such a letter must be provided by the Dean's office or equivalent; for other organizations, the letter must be signed by a corporate official.

This requirement applies also to those individuals engaged currently as the small business PD/PI on an active SBIR project. All current employment and all other appointments of the small business PD/PI must be identified in his or her Biographical Sketch required as part of the application. Be certain that correct beginning and ending dates are indicated for each employment record listed.

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 not simultaneously submit identical/essentially identical applications under both this SBIR Parent funding opportunity and any other HHS FOA, including the current STTR Parent FOA. The NIH will accept as many "different" applications as the applicant organization chooses. However, the NIH will not accept similar grant applications with essentially the same research focus from the same applicant organization. This includes derivative or multiple applications that propose to develop a single product, process or service that, with non-substantive modifications, can be applied to a variety of purposes.

It is unlawful to enter into contracts or grants requiring essentially equivalent work or effort. Essentially equivalent work or effort occurs when (1) substantially the same research is proposed for funding in more than one contract proposal or grant application submitted to the same Federal agency; (2) substantially the same research is submitted to two or more different Federal agencies for review and funding consideration; or (3) a specific research objective and the research design for accomplishing an objective are the same or closely related in two or more proposals or awards, regardless of the funding source. If there is any question concerning essentially equivalent work or effort, it must be disclosed to the soliciting agency or agencies before award.

Only one Phase II award may be made for a single SBIR/STTR project.

You may submit a Phase II application either before or after expiration of the Phase I budget period, unless you elect to submit a Phase I and Phase II application concurrently under the Fast-Track procedure. To maintain eligibility to seek Phase II support, a Phase I grantee organization should submit a Phase II application within the first six receipt dates following the expiration of the Phase I budget period.

Section IV. Application and Submission Information

To download a SF424 (R&R) Application Package and SF424 (R&R) SBIR/STTR 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:

• Grants.gov (http://www.grants.gov/GetStarted) and
• eRA Commons (http://era.nih.gov/ElectronicReceipt/preparing.htm)

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

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

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

• Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants.gov registration process.
• If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration.
• The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business days.
• Direct questions regarding Grants.gov registration to:
  Grants.gov Customer Support
  Contact Center Phone: 800-518-4726
  Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
  Email [email protected]

2) Organizational/Institutional Registration in the eRA Commons

• To find out if an organization is already Commons-registered, see the "List of Grantee Organizations Registered in NIH eRA Commons.
• Direct questions regarding the Commons registration to:
  eRA Commons Help Desk
  Phone: 301-402-7469 or 866-504-9552 (Toll Free)
  TTY: 301-451-5939
  Business hours M-F 7:00 a.m. 8:00 p.m. Eastern Time
  Email [email protected]

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

• The individual(s) designated as PD/PIs on the application must also be registered in the NIH eRA Commons and be assigned the PI role in the eRA Commons prior to the submission of the application. It is not necessary for PDs/PIs to register with Grants.gov.
• Each PD/PI must hold a PD/PI account in the Commons. Applicants should not share a Commons account for both an Authorized Organization Representative/Signing Official (AOR/SO) role and a PD/PI role; however, if they have both a PD/PI role and an Internet Assisted Review (IAR) role, both roles should exist under one Commons account.
• When multiple PDs/PIs are proposed, all PDs/PIs at the applicant organization must be affiliated with that organization. When PDs/PIs are located at another institution, only the contact PI (the PI named on the SF424 (R&R) Cover) must be affiliated with the applicant small business concern; other PD/PIs need not be affiliated with the applicant organization, but must be affiliated with their own organization to be able to access the Commons.
• This registration/affiliation must be done by the AOR/SO or their designee who is already registered in the Commons.

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 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) SBIR/STTR Application Guide for this FOA using the Apply for Grant Electronically button in this FOA or 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 301-710-0267, Email: [email protected].

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

2. Content and Form of Application Submission

Prepare all SBIR applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) SBIR/STTR Application Guide instructions.

The SF424 (R&R) SBIR/STTR 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 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. 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
Research & Related Budget
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
SBIR/STTR Information

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

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. For SBIR, the contact PI must be from the small business. All funding for SBIR projects goes to the small business awardee, so funding for PD/PIs from other organizations must be requested via a subcontract with the small business using the Research & Related Subaward Budget Attachment(s) Form. 

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.

3. Submission Dates and Times

See Section IV.3.A. for details.

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

Opening Date:  February 25, 2007 (Earliest date an application may be submitted to grants.gov)
Letters of Intent Receipt Date(s): March 25, 2007
Application Receipt Date: April 25, 2007
Peer Review Date(s): June/July 2007
Council Review Date(s): August 2007
Earliest Anticipated Start Date(s): December 2007

3.A.1. Letter of Intent

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

• Descriptive title of proposed research
• Name, address, and telephone number of the PD/PI
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

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 Institute and Center (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
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3039
Bethesda, MD 20892-9304
[For express mail, use Rockville, MD 20852-1705]
Telephone: (301) 443-9737
FAX: (301) 443-6077
Email: [email protected]

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants may use the Apply for Grant Electronically button in this FOA or link to 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 [email protected] when the application has been submitted.  Please include the FOA number and title, and 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 to determine if any further action is necessary.

• If everything is acceptable, no further action is necessary. The application will automatically move forward for processing by the Division of Receipt and Referral, Center for Scientific Review, NIH, after two business days.
• Prior to the submission deadline, the AOR/SO can Reject the assembled application and submit a changed/corrected application within the two day viewing window. This option should be used if the AOR/SO determines that warnings should be addressed or if information was lost or compromised during transmission. Reminder: warnings do not stop further application processing. If an application submission results in warnings (but no errors) it will automatically move forward after two business days if no action is taken.  Please remember that some warnings may not be applicable or may need to be addressed after application submission.
• If the two day window falls after the submission deadline, the AOR/SO will have the option to Reject the application if, due to an eRA Commons or Grants.gov system issue, the application does not correctly reflect the submitted application package (e.g., some part of the application was lost or didn t transfer correctly during the submission process). The AOR/SO should first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.
• If the AOR/SO chooses to Reject the image after the submission deadline for a reason other than an eRA Commons or Grants.gov system failure, a changed/corrected application still can be submitted but it will be subject to the NIH late policy guidelines and may not be accepted. The reason for this delay should be explained in the cover letter attachment.
• Both the AOR/SO and PD/PI will receive e-mail notifications when the application is rejected or the application automatically moves forward in the process after two days.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review (CSR) and responsiveness by NIAAA. Incomplete and non-responsive applications will not be reviewed.

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 PD/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 using the standard NIH, CDC, and FDA SBIR submission dates of April 5, August 5, and December 5 (or May 1, September 1, and January 2 for NIH AIDS and AIDS-related SBIR applications). 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 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 each 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.

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

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) SBIR/STTR Application Guide are to be followed, with the following requirements.

SBIR Phase I applications:

• Although preliminary data are not required, they may be included.
• Items 2-5 of the Research Plan component may not exceed 15 pages, including tables, graphs, figures, diagrams, and charts.
• The Biographical Sketch is limited to a maximum of 4 pages for each senior/key person. (This includes the table at the top of the first page).
• There is no further limitation on the total number of pages for the entire Phase I application; however, applicants are encouraged to be succinct.

SBIR Phase II applications and Phase II Competing Renewals:

• Items 2-5 of the Research Plan component may not exceed 25 pages, including tables, graphs, figures, diagrams, and charts.
• The Biographical Sketch is limited to a maximum of four (4) pages for each senior/key person. (This includes the table at the top of the first page.)
• The Phase II application must present a Commercialization Plan (maximum 15 pages) that addresses specific points as described in the SF424 (R&R) SBIR/STTR Application Guide and the SBIR/STTR Information component.
• There is no further limitation on the total number of pages for the entire Phase II application; however, applicants are encouraged to be succinct.

SBIR Fast-Track applications:

• The NIH Fast-Track application is a single application consisting of Phase I and Phase II activities. See Section 1.3.2., Fast-Track Applications, of the SF424 (R&R) SBIR/STTR Application Guide.
• The Phase I portion of a Fast-Track must specify clear, measurable goals (milestones) that should be achieved prior to initiating Phase II work.
• The Fast-Track application must present a Commercialization Plan (maximum 15 pages) that addresses specific points as described in the SF424 (R&R) SBIR/STTR Application Guide.
• Items 2-5 of the Research Plan component may not exceed 25 pages. That is, the combined Phase I and Phase II plans for Fast-Track applications (for Items 2-5) must be contained within the 25-page limitation.

Warning: Please be sure that you observe the total 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.

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.

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. Phase I SBIR/STTR Appendix materials are not permitted unless specifically requested by NIH.

Plan for Sharing Research Data

Applicants requesting $500,000 or more in direct costs in any year must include a brief one paragraph description of how final research data will be shared, or explain why data-sharing is not possible. The specific nature of the data to be collected will determine whether or not the final dataset may be shared. If the final data are not amenable to sharing (for example human subjects concerns, Small Business Act provisions, etc.), this must be explained in the application. Applicants are encouraged to discuss their data-sharing plan with the Institute/Center (IC) staff likely to accept assignment of their application.

The reasonableness of the data sharing plan or the rationale for not sharing research data may 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. For more information on data sharing see http://grants.nih.gov/grants/policy/data_sharing/.and http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm. (See FAQ #13.)

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 (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources 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 that are complete and responsive to this funding opportunity 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:

• Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score.
• Receive a written critique.
• Receive a second level of review by NIAAA Advisory Council

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

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

The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. The scientific review group will address and consider each of these criteria in assigning the application's overall score, weighting them as appropriate for each application.

• Significance
• Approach
• Innovation
• Investigator
• Environment

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.

Applicants should include information in relevant sections of the grant application that addresses the questions for each review criterion below.

All SBIR Applications

Significance: Does the proposed project have commercial potential to lead to a marketable product, process or service? Does this study address an important problem? What may be the anticipated commercial and societal benefits that may be derived from the proposed research? 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? Does the application lead to enabling technologies (e.g., instrumentation, software) for further discoveries? Will the technology have a competitive advantage over existing/alternate technologies that can meet the market needs?

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? Is the proposed plan a sound approach for establishing technical and commercial feasibility? Are the milestones and evaluation procedures appropriate? 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?

Investigator(s): 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 PD/PI(s) and other researchers, including consultants and subcontractors (if any)? Do the PD/PIs and investigative team bring complementary and integrated expertise to the project (if applicable)? Are the relationships of the key personnel to the small business and to other institutions appropriate for the work proposed?

Environment: Do(es) the scientific and technological 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? Is there sufficient access to resources (e.g., equipment, facilities)?

Phase II Applications

In addition to the above review criteria:

1. How well did the applicant demonstrate progress toward meeting the Phase I objectives, demonstrating feasibility, and providing a solid foundation for the proposed Phase II activity?

2. Did the applicant submit a concise Commercialization Plan that adequately addresses the specific areas described in the SF424 (R&R) SBIR/STTR Application Guide and the SBIR/STTR Information component?

3. Does the project carry a high degree of commercial potential, as described in the Commercialization Plan?

Phase I/Phase II Fast-Track Application Review Criteria

For Phase I/Phase II Fast Track applications, the following criteria also will be applied:

1. Does the Phase I application specify clear, appropriate, measurable goals (milestones) that should be achieved prior to initiating Phase II?

2. Did the applicant submit a concise Commercialization Plan that adequately addresses the specific areas described in the SF424 (R&R) SBIR/STTR Application Guide and the SBIR/STTR Information component?

3. To what extent was the applicant able to obtain letters of interest, additional funding commitments, and/or resources from the private sector or non-SBIR/STTR funding sources that would enhance the likelihood for commercialization?

4. Does the project carry a high degree of commercial potential, as described in the Commercialization Plan?

Phase I and Phase II Fast-Track applications that satisfy all of the review criteria will receive a single rating.

For Fast-Track applications, the Phase II portion may not be funded until a Phase I final report and other documents necessary for continuation have been received and assessed by program staff that the Phase I milestones have been successfully achieved. Items 2-5 of the Research Plan may not exceed 25 pages. That is, the combined Phase I and Phase II plans for a Fast-Track application (for Items 2-5) must be contained within the 25-page limitation.

Phase II Competing Renewal Applications

In addition to the above review criteria described under All SBIR Applications, the following items will be applied to ALL Phase II competing renewal applications in the determination of scientific merit and the priority score.

1. Does the activity as proposed address issues related to Federal regulatory approval processes?

2. Did the applicant submit a concise Commercialization Plan that adequately addresses the specific areas described in the SF424 (R&R) SBIR/STTR Application Guide and the SBIR/STTR Information component?

3. Does the project carry a high degree of commercial potential as described in the Commercialization Plan?

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 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 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 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.

2.C. Sharing Research Data

The reasonableness of the data sharing plan or the rationale for not sharing research data may 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 funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing

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/grants/policy/nihgps_2003/NIHGPS_Part7.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 will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. 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/her Summary Statement (written critique) via the 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 also 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

NIH requires that SBIR/STTR grantees submit the following reports within 90 days of the end of the grant budget period unless the grantee is under an extension.

Financial Status Report (OMB 269, http://www.whitehouse.gov/omb/grants/grants_forms.html)
Final Progress Report
Final Invention Statement and Certification (HHS 568)
Annual Invention Utilization Reports
Final Cash Transaction Report (PSC 272, http://www.dpm.psc.gov/Reports.aspx)
Phase II Data Collection Requirement for Government Tech-Net Database  (http://technet.sba.gov)
Failure to submit timely final reports may affect future funding to the organization or awards with the same PD/PI.

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:

For preclinical questions:

Mark Egli Ph.D
Division of Neuroscience and Behavior
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 2053
Bethesda,  MD 20892-9304
[For express mail, use Rockville, MD 20852-1705]
Phone: 301 594-6382
FAX: 301 443-1650
Email: [email protected]

For clinical questions:

Joanne B. Fertig, Ph. D.
Division of  Treatment and Recovery Research
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 2043
Bethesda,  MD 20892-9304
{For express mail, use Rockville, MD 20852-1705]
Phone: 301 443-0635
FAX: 301 443-8774
Email: [email protected]

2. Peer Review Contacts:

Abraham Bautista, Ph.D.
Chief, Extramural Project Review Branch
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3039
Bethesda, MD 20892-9304
[For express mail, use Rockville, MD 20852-1705]
Telephone: (301) 443-9737
FAX: (301) 443-6077
Email: [email protected]

3. Financial or Grants Management Contacts:

Judy Fox
Chief, Grants Management Branch
Office of Extramural Activities
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3023
Bethesda, MD 20892-9304
[For express mail, use Rockville, MD 20852-1705]
Phone: (301) 443-4704
Fax (301) 443-3891
Email: [email protected]

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 scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The 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 the 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); 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.