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: Medications Development for the Treatment of Alcoholism (STTR [R41/R42])

Announcement Type

This is a reissue and modification of RFA-AA-04-002 which was previously released December 4, 2003.

Update: The following update relating to this announcement has been issued:

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 SF 424 (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.

Two steps are required for on time submission:

1) The application must be submitted to Grants.gov by 5:00 p.m. local time (of the applicant institution/organization) on the submission date (see “Key Dates” below).

2) Applicants must complete a verification step in the eRA Commons within two business days of notification from NIH. Note: Since email can be unreliable, it is the responsibility of the applicant to periodically check on their application status in the Commons.

Request For Applications (RFA) Number: RFA-AA-06-007

Catalog of Federal Domestic Assistance Number(s)
93.273

Key Dates
Release/Posted Date: January 20, 2006
Opening Date: February 17, 2006
Letters of Intent Receipt Date(s): March 18, 2006
Application Submission Dates(s): April 18, 2006
Peer Review Date(s): June/July 2006
Council Review Date(s): October 2006
Earliest Anticipated Start Date: December 2006.
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: April 19, 2006

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is seeking research grant applications on the development of medications for alcohol abuse/dependence and alcohol-related diseases. 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. Applications are also encouraged to develop and test agents for the treatment of acute alcohol withdrawal and alcohol intoxication.
Evaluations of pharmacological agents to treat alcohol-induced diseases, such as alcoholic liver diseases, are encouraged as well.

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. Sending an Application 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

PURPOSE OF THIS FOA

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 and alcohol-related diseases. Investigations are needed on pharmacological agents that prevent or reduce alcohol intake. Applications are also encouraged to develop and test agents for the treatment of acute alcohol withdrawal and alcohol intoxication. Evaluations of pharmacological agents to treat alcohol-induced diseases, such as alcoholic liver disease, are encouraged as well.

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, many of which may 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 "magic bullet" for alcoholism treatment, but appears to have a moderate effect in reducing drinking, particularly in reducing relapse to heavy drinking (Volpicelli et al., 1997; 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 may 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 for 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; Scott et al., 2005). 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 behavior. The serotonin 3 (5-HT3) receptor has been shown to regulate release of dopamine in the mesolimbic area, particularly in the nucleus accumbens. Ondansetron, a 5-HT3 antagonist, has been demonstrated to reduce desire to drink in humans and to augment stimulant and sedative effects of alcohol (Johnson et al., 1993; Swift et al., 1996). In a 12-week trial of ondansetron the compound 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., 2000a; Ait-Daoud et al., 2001).

Results of selective serotonin reuptake inhibitors (SSRIs) in human alcohol trials have yielded inconsistent results (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, development and evaluation of new, more efficacious medications remains a high priority. Several promising pharmacological 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; Le et al., 2000; Richter et al., 2000); opioid subtype receptor antagonists such as delta2 antagonist naltriben (June et al., 1999); synthetic neurosteroids (Morrow et al., 1999); FG 5974 (and its analogues) a 5-HT1A/5HT2A antagonist (Roberts et al., 1998); agents with selective affinity to GABAA alpha1 or GABAA alpha 5 receptor subunits (June et al., 2001, Harvey et al., 2002) and, an mGluR5 antagonist (Backstrom et al. 2004).

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.

For pharmacological management of acute alcohol withdrawal, benzodiazepines have been the most widely used medication over the past two decades. They have consistently been demonstrated to assuage many symptoms of withdrawal (Mayo-Smith, 1997). In spite of their efficacy, benzodiazepines have adverse effects including memory impairment, drowsiness, lethargy, and cognitive problems; development of compounds with fewer or milder side effects remains desirable.

Finally, progress has been made in elucidating the mechanisms of alcohol-induced organ damage. In particular, several primary factors underlying the pathogensis of alcoholic liver disease have been identified including cytokines and reactive oxygen species (ROS)

(Tsukamoto and Lu, 2001). For example, the administration of antibodies against the proinflammatory tumor necrosis factor (TNF) attenuated alcohol-induced liver injury in rats (Iimuro et al., 1997). A later study showed an absence of alcohol liver injury in TNF-R1 knockout mice (Yin et al., 1999). ROS, generated by the metabolism of alcohol and causing liver damage (Tsukamoto and Lu, 2001), are quickly inactivated by antioxidants such as glutathione and vitamins A and E. Antioxidants, such as S-adenosyl-L- methionine (SAMe), have also been shown to reduce alcohol-induced liver injury in animals. Potential new treatments of alcoholic liver disease include antioxidants as well as other agents including phosphatidylcholine, a phospholipid; pirfenidone, a new broad- spectrum anti-fibrotic agent; and metformin, an insulin-sensitizing agent (Lieber, 2001; Miric et al., 2001; Tsukamoto and Lu, 2001).

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. Pharmacological agents of interest can be categorized by function as follows:

-Agents to reduce drinking.

-Agents to prolong abstinence.

- Agents to decrease craving or urge to drink.

- Agents to diminish drinking by alleviating co-occurring psychiatric pathology and other drug use.

- Agents to treat alcohol-associated liver disease and other end-organ diseases, such as pancreatitis, cardiomyopathy, and bone disease.

- Agents to treat acute alcohol withdrawal.

- Agents to induce sobriety in intoxicated individuals.

Many important clinical priorities and issues exist for these classes of pharmacological agents and are identified, but not limited, to the following:

New and existing pharmacological agents and combinations of agents need to be identified and evaluated in conjunction with behavioral therapies for alcoholism treatment. Optimal dosing regimens and length of treatment need to be established. Although NIAAA has supported projects on the efficacy of the opioid antagonist naltrexone, the therapeutic potential of other pharmacological agents in the opioid class is a current research priority. In addition to opioid antagonists, the therapeutic potential of other types of agents needs to be assessed. Among these are agents that interact with the serotonergic, dopaminergic, glutamatergic, GABAergic, NPY, cannabinoid, and HPA systems as well as herbal preparations.

- Development of pharmacological agents to attenuate negative symptoms of chronic drinking, sometimes referred to as the "protracted withdrawal" syndrome. Research on potential pharmacological treatment of this phenomenon has been quite limited, due to failure to specify cardinal symptoms associated with sustained sobriety by alcoholics. Research is needed to establish operational definitions of this event as is research on agents to reduce the severity of protracted symptoms.

-Factors influencing clinical efficacy of medications to treat alcohol abuse and dependence can be identified using human laboratory behavioral pharmacology paradigms. Prior to beginning phase 2 clinical trials, potential medications can be screened in the laboratory to determine their: 1) ability to reduce craving, 2)ability to alter stimulus effects of ethanol (including ‘stimulatory’ effect), 3) likelihood of adverse events, especially in the presence of alcohol, 4)

pharmacokinetics alone and in combination with other drugs, especially alcohol,and 5) optimal dosing regimens. Studies are sought which develop and expand use of these human laboratory procedures.

- Development of medications to treat alcoholic liver disease and other alcohol-related, end-organ diseases. These may include agents that inactivate excess ROS or alter the production or clearance of cytokines. In reducing the high mortality from alcoholic hepatitis and cirrhosis, potential medications that prevent necrosis/inflammation and avert or reverse the progression of fibrosis are of high priority.

Other potential agents include those that are effective in treating alcohol-induced portal hypertension, pancreatitis, and bone disease.

- Use of genomics, proteomic and metabolomic approaches to identify molecular targets for medications development for alcohol abuse susceptibility, alcohol dependence, alcohol consumption, withdrawal, and relapse, and alcohol-associated medical conditions.

- Synthesis of new compounds based on the molecular structure of receptors, ion channels, and sites of cellular signal transduction mechanisms involved in alcohol's actions on the nervous system.

- Screening of existing "off the shelf" compounds for properties associated with therapeutic efficacy for treating alcohol abuse and alcohol related conditions.

- Development of alternative medications to treat acute alcohol withdrawal. Also, assuming the "kindling" effect (the severity of withdrawal symptoms increases after repeated withdrawal episodes) has clinical relevance (Becker, 1998), development of medications to treat withdrawal that also limit kindling.

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. American Journal of Psychiatry 156:1758-1764.

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

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

Becker, H.C. (1998) Kindling in alcohol withdrawal. Alcohol Health and Research 22:25-33.

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. The Journal of Alcohol and Alcoholism 35:587-593.

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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 Psychiat 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. Journal of Neuroscience 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. Journal of Clinical Psychopharmacology 21:287-292.

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

Iimuro, Y., Gallucci, R.M., Luster, M.I., Kono, H., and Thurman, R.G. (1997) Antibodies to tumor necrosis factor alpha attenuate hepatic necrosis and inflammation caused by chronic exposure to ethanol in the rat. Hepatology 26: 1530-1537.

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. Alcoholism: Clinical and Experimental Research 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 Neuroscience 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. Proceeding of the National Academy of Sciences of the USA 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. Alcoholism: Clinical and Experimental Research 20:1534-1541.

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 England Journal of Medicine 345:1734-1739.

Lieber, C.S. (2001) Liver diseases by alcohol and hepatitis C: Early detection and new insights in pathogenesis lead to improved treatment. The American Journal on Addictions 10(Supplement): 29-50.

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. Alcoholism: Clinical and Experimental Research 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 Opinion Emerging Drugs 10(2): 323-343.

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

Mayo-Smith, M.F. (1997) Pharmacological management of alcohol withdrawal: A meta-analysis and evidence-based practice guideline. Journal of the American Medical Association278:144-151.

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.

Miric, G., Dallemagne, C., Endre, Z., Margolin, S., Taylor, S.M., and Brown, L. (2001) Reversal of cardiac and renal fibrosis by pirfenidone and spironolactone in streptozotocin-diabetic rats. British Journal of Pharmacology 133:687-694.

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. Alcoholism: Clinical and Experimental Research 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? Alcoholism: Clinical and Experimental Research 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. Archives of General Psychiatry 49:881-887.

Pettinati, H.M. (1996) Use of serotonin selective pharmacotherapy in the treatment of alcohol dependence. Alcoholism: Clinical and Experimental Research 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: Clinical and Experimental Research 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. Journal of Clinical 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. Alcoholism: Clinical and Experimental Research 24:1765-1772.

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. Biological Psychiatry 40:514-521.

Tsukamoto, H. and Lu, S.C. (2001) Current concepts in the pathogenesis of alcoholic liver injury. FASEB Journal 15: 1335-1349.

Volpicelli, J.R., Alterman, A.I., Hayashida, M. and O'Brien, C.P. (1992) Naltrexone in the treatment of alcohol dependence. Archives of General 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. Archives of General Psychiatry 54:737-742.

Yin, M., Wheeler, M.D., Kono, H., Bradford, B.U., Gallucci, R.M., Luster, M.I., and Thurman, R.G. (1999). Essential role of tumor necrosis factor alpha in alcohol-induced liver injury in mice. Gastroenterology 117: 942-952.

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

Section II. Award Information

1. Mechanism(s) of Support

This FOA (RFA-AA-06-007) will use the Small Business Technology Transfer (STTR [R41/R42]) 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.

A parallel FOA of identical scope (RFA-AA-06-006) utilizes the Small Business Innovation Research (SBIR [R43/R44]) grant mechanisms. Applicants may not simultaneously submit identical/essentially identical applications under both this funding opportunity and another HHS FOA, including the current SBIR or STTR Parent FOAs.

Phase II applications in response to this funding opportunity will only be accepted as competing renewals (formerly “competing continuations”) of previously funded Phase I STTR awards. 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.

The applicant SBC will be solely responsible for planning, directing, and executing the proposed project. Future unsolicited, competing renewal applications based on this project will compete with all STTR applications and will be reviewed according to the customary peer review procedures. Applications that are not funded in the competition described in this FOA may be submitted as NEW applications through
Grants.gov/Apply using the standard NIH STTR submission dates of April 1, August 1, and December 1 (or January 2, May 1, and September 1 for NIH AIDS and AIDS-related STTR applications).

This funding opportunity uses just-in-time concepts. The modular budget format is no longer accepted for STTR 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.

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 STTR 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 and up to 2 years may be requested for Phase II. For Phase II Competing Renewals requests should not exceed $750,000 total costs per year for up to three years. Total costs include direct costs, Facilities & Administrative (F&A)/indirect costs, and fee.”

NIAAA, intends to commit up to $1 million dollars in FY 06 to fund 2-4 Phase I and/or Phase II or, Phase II Competing Renewal applications under the STTR 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. At this time, it is not known if competing renewal applications will be accepted and/or if this FOA will be reissued.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

Only United States small business concerns (SBCs) are eligible to submit STTR applications. A small business concern is one that, at the time of award for both Phase I and Phase II STTR 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 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 13 C.F.R. 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 Title 13 Code of Federal Regulations (CFR) Part 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 STTR awardee organization must be space that is available to and under the control of the STTR awardee for the conduct of its portion of the proposed project.

Title 13 C.F.R. 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 STTR 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, 13C.F.R. 121.106 – Small Business Size Regulations.

All STTR 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 STTR award until the SBA provides a determination.

1.B. Eligible Individuals

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

For a STTR application, the Project Director/Principal Investigator (PD/PI) may be employed with the SBC or the participating non-profit research institution as long as s/he has a formal appointment with or commitment to the applicant SBC, which is characterized by an official relationship between the SBC and that individual.

As defined in 42 CFR 52, the PD/PI is the “single individual designated by the grantee in the grant application … who is responsible for the scientific and technical direction of the project.” When the proposed PD/PI clearly does not have sufficient qualifications to assume this role, the application is not likely to receive a favorable evaluation.

The PD/PI must commit a minimum of 10% effort to the project and the PD/PI must have a formal appointment with or commitment to the applicant small business concern, which is characterized by an official relationship between the small business concern and that individual. Such a relationship does not necessarily involve a salary or other form of remuneration. In all cases, however, the PD/PI’s official relationship with the grantee must entail sufficient opportunity for the PD/PI to carry out his or her responsibilities for the overall scientific and technical direction of the project. Documentation (e.g., consultant, consortium and contractual arrangements) describing the official relationship of the PD/PI with the applicant small business concern should NOT be submitted with the grant application, but a copy must be furnished upon the request of the NIH awarding component.

The following are examples of situations describing the official relationship of the PD/PI with the applicant small business organization:

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

In STTR Phase I and Phase II, at least 40% of the work must be performed by the small business concern and at least 30% of the work must be performed by the single, “partnering” research institution. The basis for determining the percentage of work to be performed by each of the cooperative parties will be the total of direct and F&A/indirect costs attributable to each party, unless otherwise described and justified in Item 12, “Consortium/Contractual Arrangements,” of the PHS398 Research Plan component of the SF424 (R&R) application forms.

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. Applicants may not simultaneously submit identical/essentially identical applications under both this funding opportunity and another HHS FOA, including the current SBIR or STTR Parent FOAs.

Section IV. Application and Submission Information

Registration and Instructions for Submission via Grants.gov

To download an Application Package and 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:

PD/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 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.

To affiliate the PD/PI with the small business concern:

1. PD/PI gives Commons user ID and email address to the administrator of the applicant organization/institution. (The email address must be the one that is contained in the Personal Profile for the PD/PI.)

2. Administrator logs into the Commons. (The administrator can be the Signing Official, Administrative Official, or the Accounts Administrator.)

3. Administrator selects "Administration" tab and then "Accounts" tab.

4. Administrator selects "Create Affiliation" tab.

5. Administrator enters the Commons User ID and Email address into the appropriate fields and clicks "Submit."

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 the DUNS number and CCR registration used by an applicant small business concern. Individual DUNS and CCR registration should be used only for the purpose of personal reimbursement and should not be used on any grant application submitted to the Federal Government.

Several of the steps of the registration process could take several 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 NIH eRA 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 STTR applications using the SF424 (R&R) application forms and the SF424 (R&R) SBIR/STTR Application Guide (MS Word) or PDF) 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 “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 “Tips and Tools for Navigating Electronic Submission” on the front page of “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
Research & Related Subaward Budget Form

PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
SBIR/STTR Information

Optional Components:

PHS398 Cover Letter File

3. Submission Dates and Times

See Section IV.3.A. for details.

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

Opening Date: February 17, 2006
Letter of Intent Receipt Date: March 18, 2006
Application Submission Date(s): April 18, 2006
Peer Review Date: June/July 2006
Council Review Date: October 2006
Earliest Anticipated Start Date: December 2006

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:

Karen P. Peterson, Ph.D.
Chief, Research Policy and Special Programs Branch
Office of Scientific Affairs, NIAAA/NIH
5635 Fishers Lane MSC 9304
Bethesda, MD 20892-9304
Telephone: 301-451-3883
Fax: 301-443-7043
Email: kperterso@mail.nih.gov

3.B. Sending an Application to the NIH

Applications in response to this FOA may only be submitted to Grants.gov through Grants.gov/Apply.
PAPER APPLICATIONS WILL NOT BE ACCEPTED.

3.C. Application Processing

Applications may be submitted to Grants.gov on or after February 17, 2006 (i.e., the Opening Date on Grants.gov) and must be submitted no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission dates identified in Section IV.3.A.. If an application is not submitted by that date, the application may be delayed in the review process or not reviewed.

Upon receipt, applications will be transferred from Grants.gov to the NIH Electronic Research Administration process for validation. Both the PD/PI and the Signing Official for the organization must verify the submission via Commons within 2 business days of notification of the NIH validation.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review (CSR), NIH. Incomplete applications will not be reviewed.

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.

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.

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

All application instructions outlined in the SF424 (R&R) SBIR/STTR Application Guide (MS Word or PDF) are to be followed, with the following requirements.

Note: While each section of the Research Plan needs to eventually be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan 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.

STTR Phase I applications:

STTR Phase II applications:

STTR Fast-Track applications:

Plan for Sharing Research Data

Applicants requesting $500,000 or more in direct costs in any year should 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, if they are proprietary, this must be explained in the application. The Small Business Act requires NIH to protect from disclosure and nongovernmental use all SBIR and STTR data developed from work performed under an SBIR and STTR funding agreement for a period of four (4) years after the closeout of either a Phase I or Phase II grant unless NIH obtains permission from the awardee to disclose these data. The data rights protection period lapses only upon expiration of the protection period applicable to the SBIR and STTR award, or by agreement between the small business concern and NIH. 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

Sharing Research Resources

NIH policy requires that grant awardee 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/index.htm and 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:

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

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.

The 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.

All STTR 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, and appropriate to the aims of the project? Is the proposed plan a sound approach for establishing technical and commercial feasibility? Does the applicant acknowledge potential problem areas and consider alternative strategies? Are the milestones and evaluation procedures appropriate?

Innovation: Are the aims original and innovative? 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: Is the PD/PI appropriately trained and capable of coordinating and managing the proposed STTR? Are the investigators well suited to carry out this work? Does the investigative team bring complementary and integrated expertise to the project (if applicable)? Is the work proposed appropriate to the experience level of the PD/PI and other researchers, including consultants and subcontractors (if any)? Are the relationships of the key personnel to the small business and to other institutions appropriate for the work proposed?

Environment: Is there sufficient access to resources (e.g., equipment, facilities)? Does 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?

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?

Resubmission Applications (formerly “amended” applications)

In addition to the above criteria, the following criteria will be applied to resubmission applications.

1. Are the responses to comments from the previous scientific review group adequate?

2. Are the improvements in the resubmission application appropriate?

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 (formerly “Phase II Competing Continuation” applications)

In addition to the above review criteria described under “All STTR 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:

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: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research may be assessed by the reviewers. Is the percent effort listed for the PD/PI appropriate for the work proposed? Is each budget category realistic and justified in terms of the aims and methods?

Period of Support: The appropriateness of the requested period of support in relation to the proposed research.

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 and http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm. (See FAQ #13.)

2.D. Sharing Research Resources

NIH policy requires that grant awardee 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/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). 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.

3. Anticipated Announcement and Award Dates
Not applicable

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the 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

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:

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: jfertig@mail.nih.gov

Peter B. Silverman. Ph.D, J.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: 301 402-6966
FAX: 301 443-1650
Email: psilverm@mail.nih.gov

2. Peer Review Contacts:

Tina Vanderveen, Ph.D.
Acting Chief, Extramural Project Review Branch
Acting Director, Office of Extramural Activities
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) 443-2531
FAX: (301) 443-6077
Email: tvanderv@mail.nih.gov

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: 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 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 http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). 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 (http://publicaccess.nih.gov/publicaccess_manual.htm).

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) 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 DHHS 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. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to 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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