Release Date:  September 27, 2001

RFA:  RFA-AA-02-004

National Institute on Alcohol Abuse and Alcoholism

Letter of Intent Receipt Date:  December 28, 2001
Application Receipt Date:       January 23, 2002



The National Institute on Alcohol Abuse and Alcoholism (NIAAA) invites 
applications for grants proposing innovative basic research for the 
development of pharmacotherapeutic agents for alcoholism, alcohol abuse, and 
alcohol-related medical consequences.  Alcohol researchers have made 
significant strides in uncovering mechanisms of action and developing 
experimental models of alcoholism, alcohol abuse and associated problems. 
Although much of this work has potential implications for pharmacotherapy, 
studies are often not designed to support future therapeutic possibilities. 
To facilitate discovery of compounds having possible therapeutic efficacy we 
are requesting grant applications proposing research which: (1) elucidates 
the mechanisms of action of drugs currently believed to be effective in 
treating facets of alcohol abuse and those having effects suggestive of a 
therapeutic effect in animal and human experimental paradigms;  (2) 
identifies candidate molecular targets and promising therapeutic compounds 
based on current knowledge of alcohol’s molecular, physiological and 
behavioral mechanisms of action, or based on current understanding of the 
etiology of alcohol related disease, or based on using functional genomics 
and proteomics to identify compounds with possible therapeutic value; (3) 
develops animal and human laboratory models having high predictive validity 
for clinical problems associated with alcohol abuse with emphasis on rapid 
testing.  Proposed research may encompass any stage of the medications 
development process—from chemical synthesis, genomics, proteomics, in vitro 
pharmacological studies, and in vivo pharmacokinetic, toxicity and 
bioavailability assessment, to behavioral and physiological studies in 
rodents, non-human primates and humans.  Proposals may be hypothesis driven 
basic research studies emphasizing a particular stage in the medications 
development process, but must contain a component which clearly establishes 
relevance to other stages in the process.  Results from these studies will 
lead to integrated efforts toward developing medications for alcoholism and 
alcohol abuse.


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 Request for 
Applications (RFA), New Approaches to Developing Pharmacotherapy for 
Alcoholism, is related to one or more of the priority areas.  Potential 
applicants may obtain a copy of "Healthy People 2010" at


Applications may be submitted by domestic and foreign, for-profit and non-
profit organizations, public and private, such as universities, colleges, 
hospitals, laboratories, units of State and local governments, and eligible 
agencies of the Federal government. Racial/ethnic minority individuals, 
women, and persons with disabilities are encouraged to apply as Principal 


This RFA will use the National Institutes of Health (NIH) research project 
grant (R01), exploratory/developmental grant (R21), and small grant 
(R03)award mechanisms.  Responsibility for the planning, direction, and 
execution of the proposed project will be solely that of the applicant.  
Applicants for R01s may request support for up to 5 years.  Currently, small 
grants (R03) are limited to 2 years for up to $50,000 per year for direct 
costs, and exploratory/developmental grants (R21) are limited to $100,000 per 
year for direct costs for up to 3 years. Exploratory/developmental grants and 
small grants cannot be renewed, but grantees may apply for R01 support to 
continue research on the same topics. 

Applicants may also submit applications for Investigator-Initiated 
Interactive Research Project Grants (IRPG). Interactive Research Project 
Grants require the coordinated submission of related research project grants 
(R01) from investigators who wish to collaborate on research, but do not 
require extensive shared physical resources. These applications must share a 
common theme and describe the objectives and scientific importance of the 
interchange of, for example, ideas, data, and materials among the 
collaborating investigators. A minimum of two independent investigators with 
related research objectives may submit concurrent, collaborative, cross-
referenced individual R01 applications. Applicants may be from one or several 
institutions. Further information on these and other grant mechanisms may be 
obtained from the program staff listed in the INQUIRIES section of this RFA 
or from the NIAAA Web site 

This RFA is a one-time solicitation.  Future unsolicited competing 
continuation applications will compete with all investigator-initiated 
applications and be reviewed according to the customary peer review 
procedures.  The anticipated award date is July 1, 2002.


NIAAA intends to commit approximately $2 million in FY 2002 to fund 
approximately 6 to 10 new and/or competitive continuation grants in response 
to this RFA.  Because the nature and scope of the research proposed may vary, 
it is anticipated that the size of each award will also vary. Although the 
financial plans of NIAAA provide support for this program, awards pursuant to 
this RFA are contingent upon the availability of funds and the receipt of a 
sufficient number of meritorious applications. At this time, it is not known 
if this RFA will be reissued.



Although medications are commonly used to treat alcohol withdrawal, their use 
in treating other facets of alcoholism remains limited.  This is due, in 
part, to a limited arsenal of effective pharmacotherapy.  Since 1949, only 
disulfiram and naltrexone have been approved in the United States for 
reducing alcohol drinking in alcoholics. Identifying compounds having 
potential therapeutic efficacy for alcohol related problems can be promoted 
through a variety of basic research tactics such as elucidating the 
mechanisms of drugs already having demonstrated clinical efficacy, and using 
knowledge of neuronal pathways mediating alcohol drinking in experimental 
models to develop compounds acting on specific molecular and cellular 
targets.  Prototypes might also come from existing libraries of compounds or 
may be novel compounds developed based on rational molecular design using 
knowledge of receptor structures and ion channels involved in alcohol's 
actions on the nervous system and other organ systems.  Evaluating the 
effects of compounds having potential clinical value in experimental models 
using animal and human subjects is essential in the early stages of 
medications development, and depends on the predictive validity of the 
experimental models.  Therefore, developing effective experimental models for 
conditions associated with alcoholism and alcohol abuse is also important.

Expanding on Current Pharmacotherapy for Alcohol Drinking.

Current pharmacotherapy seeks to deter drinking by making the effects of 
alcohol ingestion aversive, or else to directly reduce alcohol consumption or 
craving by inhibiting the reinforcing effects of alcohol.  The dysphoric 
reaction which occurs when alcohol is ingested after taking the aldehyde 
dehydrogenase (ALDH) inhibitor disulfiram is believed to deter subsequent 
drinking in some alcoholics. Disulfiram’s efficacy may be impeded by aversive 
side effects and the extensive process of bioactivation required to produce 
adequate ALDH inhibition, particularly in those having liver damage.  
Nevertheless, evidence that an inactive ALDH allele may protect against 
developing alcohol abuse and alcoholism justifies further research on 
compounds which inhibit ALDH.  

Studies suggest the opioid antagonist naltrexone reduces alcohol euphoria, 
craving, and relapse in human alcoholics, but whether naltrexone’s 
therapeutic efficacy is entirely mediated by blocking alcohol’s effects on 
the endogenous opioid system remains an open question. Naltrexone reduces a 
variety of positively reinforced ingestive and non-ingestive behaviors in 
laboratory studies which suggests naltrexone’s effects may not be specific to 
alcohol.  The homotaurine derivative acamprosate has performed successfully 
in clinical trials, and reduces alcohol drinking in animal models, but its 
precise mechanism of action remains unclear.  Earlier studies suggested 
acamprosate interacts with GABA receptor function.  Recent studies suggest 
acamprosate interacts with NMDA receptor mediated glutamatergic transmission 
in cortical brain regions, although this conclusion has been questioned. 
Basic research clarifying the mechanism of known effective compounds will 
lead to identifying additional agents having similar action which can then be 
assessed for effects on alcohol related characteristics. 

Identifying New Therapeutic Compounds

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 emerge from 
further research on known ethanol targets, or may occur by identifying 
possible therapeutic targets and prototype drug candidates through research 
on systems and mechanisms 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.

Another approach might be to target neurotransmitters and neuropeptides 
associated with neuronal circuits underlying alcohol dependence and craving 
or by directly counteracting the actions of alcohol at various ethanol-
sensitive sites.  Membrane proteins, including voltage-gated calcium channels 
and ligand-gated receptor/channel complexes (e.g., GABA, glycine, NMDA, 5-HT, 
nicotinic cholinergic receptors), have proven to be sensitive targets of 
alcohol action.  Effects of alcohol on such proteins have been studied 
extensively, and analyzed with prototype agonists and antagonists. Receptor 
expression, distribution, post-translational modifications such as 
phosphorylation, and structural remodeling may account for acute sensitivity 
to alcohol as well as adaptive responses during long-term exposure, and 
present another possible target for therapeutic medications. 

Molecular and structure-function research approaches may define how ethanol 
interacts with membrane proteins and may support the feasibility of 
developing antagonists which directly block alcohol’s action on cell 
membranes.  Initial studies suggest that certain amino acid residues on 
glycine and GABA receptors are especially important in determining how these 
proteins respond to ethanol.  Related studies propose that ethanol inserts 
into hydrophobic pockets within the protein, or at the protein/lipid 
interface, thereby altering protein structure and functional interactions 
with receptor ligands.  The long chain alcohol 1-octanol has been shown to 
abolish the detrimental effects of ethanol on cell-cell adhesion and 
consequent teratological damage by blocking ethanol action at one such site.  
Similar research on other types of receptors and channels may reveal a common 
set of interactions between alcohol and membrane proteins. Understanding 
these interactions will promote designing specific agents to counteract acute 
and chronic actions of alcohol.   Likewise, molecular modeling will define 
the extent to which alcohol affects the structure and pharmacological 
properties of potential therapeutic agents.  

Signal transduction cascades and intracellular diffusible messengers mediate 
the effects of acute ethanol exposure and may participate in adaptive 
responses to chronic ethanol exposure.  These systems exert widespread 
actions on cell metabolism and gene transcription, and they provide intricate 
pathways for feed-forward and feedback regulation of channels and receptors.  
Alcohol is known to affect PKA, PKC, Ca, PLC, and calcium-calmodulin kinase 
signaling systems.   Phosphorylation of membrane proteins by appropriate 
kinases may account for time-dependent, model-specific, or tissue-specific 
differences in response to alcohol.  PKC-epsilon activity has been reported 
to mediate up-regulation of N-type calcium channels in response to sustained 
alcohol exposure. Mice lacking PKC-epsilon display increased sensitivity to 
ethanol’s behavioral and biochemical effects, and reduced ethanol self-
administration and handling induced withdrawal convulsions.  Reduced cAMP-PKA 
signaling in mice engendered by targeted disruption of the Gs-alpha allele is 
associated with increased sensitivity the sedative effects of ethanol and 
decreased alcohol consumption.  Mice lacking a regulatory subunit of PKA 
receptors are resistant to alcohol sedation and voluntarily consume more 
alcohol than normal mice.  Further research suggesting ways to selectively 
modify PKC-epsilon and PKA signaling mechanisms pharmacologically may lead to 
medications which effectively reduce alcohol drinking in alcoholics.  Lesser-
known or more recently-discovered signaling systems (e.g., nitric oxide, 
endocannibinoids) also offer prime opportunities for medications development.  
Extending studies of signaling systems to periods of alcohol withdrawal and 
beyond may also prove fruitful.

Further research on cellular structures and neuronal circuits having 
channels, receptors, and signaling systems with specialized functions 
relevant to alcohol action may reveal possible targets for medications 
development.  Transmitter and receptor interactions in the ventral tegmental 
area and nucleus accumbens are of interest for their proposed role in alcohol 
reinforcement. Local circuits in cerebellum and hippocampus involve 
transmitters and modulators that also have demonstrated involvement in 
alcohol effects.  Medications development in this context may address subtle 
aspects of intracellular communication and regulation, with resulting effects 
on particular facets of alcohol action such as ataxia, learning, memory, or 

Advances in molecular genetics (e.g., microarray analysis, targeted 
mutations, proteomics) offer a powerful approach for broad-spectrum scanning 
of participants in the adaptive process.  Individual gene clusters or 
functionally-related proteins 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 recruited as alcohol 
dependence develops.  Receptors or pathways involved in alcohol drinking and 
other alcohol effects can be disabled selectively with targeted knockout 
strategies. An unanswered question facing medical treatment concerns 
potential targets for modifying neurological changes underlying craving and 
alcohol-seeking after periods of prolonged abstinence. 

Developing Experimental Models

Experimental research on pharmacotherapy for alcohol abuse and alcoholism 
rests on the quality of the experimental models.  Research using animal 
subjects can address many facets of alcoholism including inherited 
predisposition, positive and negative reinforcing effects, subjective 
effects, relapse, and neuroadaptive consequences of exposure and abstinence.  
Well designed experiments can aid in developing drugs tailored toward 
specific facets of alcohol abuse. 

Non-human primate experiments may be especially desirable for research on 
pharmacotherapy for alcoholism.  In addition to being genetically and 
physiologically more similar to humans, the longer lifespan of the monkey 
permits assessment of long term treatment efficacy, dose-effect 
manipulations, and assessment of combined pharmacotherapy.   Using non-human 
primates also makes it possible to examine more complex behaviors (choice, 
cognition, social behavior) which may be directly relevant to the clinical 
situation.  Extrapolating from animal studies to humans may be facilitated by 
studying multiple animals species (e.g., rodents and non-human primates), and 
by studying humans using comparable paradigms.  Clinical trials would be 
justified when findings from preclinical human experiments are consistent 
with those from animal studies.  There are many experimental models used in 
human laboratory studies which parallel those commonly used in animal studies 
of pharmacotherapeutic mechanisms (e.g., experimental alcohol self-
administration and choice, ethanol discrimination training, laboratory 
measures of impulsivity, aggression, and cognition).  Using these laboratory 
procedures to examine mechanisms underlying alcohol’s behavioral effects in 
humans will provide valuable information for planning clinical assessments.

Although well developed behavioral models of clinical conditions are 
essential for preclinical studies, many require a great deal of time, and may 
not be ideal for screening compounds.  Hence, it is desirable to develop 
rapid assessments which are strongly associated with facets of alcohol abuse 
as modeled in more extensive analyses. Such measures need not have apparent 
face validity as long as they have high predictive validity, and are 
relatively rapid and easy to conduct.  Agents affecting alcohol responses in 
rapid assessment paradigms would be candidates for subsequent tests in more 
informative experiments which more directly reflect clinical situations.

Alcohol Associated Dysfunction

Research leading to effective pharmacotherapy for consequences of alcohol 
abuse (liver disease, birth defects, pancreatitis, hypertension, 
cardiomyopathy, and cognitive impairment) may incorporate many of the 
strategies discussed above. The possibility of protecting against alcohol-
related birth defects and alcohol induced brain damage through 
pharmacotherapy is recent research showing that low doses of the long chain 
alcohol 1-octanol antagonizes ethanol inhibition of L1-mediated cell 
adhesion, and prevents subsequent dysmorphy and apoptotic cell death 
associated with alcohol exposure in mice.  Prenatal administration of two 
active peptide fragments derived from ADNF to alcohol treated pregnant mice 
significantly increased the number of surviving fetuses and prevented reduced 
brain and body mass.  Further research is needed to identify substances which 
protect against the destructive consequences alcohol exposure during 

Experimental models have been important tools in identifying brain damage and 
neurological dysfunction which is associated with a wide spectrum of 
cognitive disturbances associated with long-term alcohol exposure.  Although 
laboratory learning tasks are widely available which are sensitive to effects 
of acute and chronic ethanol exposure, these paradigms have not been 
effectively used to test drugs which may improve cognitive function in 
alcoholics. Approaches to treating age related cognitive deficits and 
intellectual disabilities may be applicable.  More research is needed to 
identify pharmaceutical interventions which can significantly reverse or 
protect against temporary and lasting cognitive impairment associated with 
alcohol ingestion. Examining transduction signal pathways involving 
neurotrophic factors and those leading to apoptosis as the brain reorganizes 
during prolonged alcohol exposure has potential for uncovering novel ways of 
counteracting alcohol-related neurotoxicity. 

A similar approach can be used to develop new treatments for alcohol-induced 
tissue injury.  For example, advances have been made in understanding some of 
the factors contributing to alcoholic liver disease.  Reactive oxygen species 
(ROS)resulting from alcohol metabolism have been shown to damage liver 
tissue.  Increased and stable synthesis of the antioxidant superoxide 
dismutase (SOD) prevent ROS production and reduce injury due to oxidant 
stress.  Intravenous administration of adenovirus containing the gene for SOD 
increases hepatic expression of SOD and reduces liver injury and pathology in 
rats.  These findings raise the possibility using gene delivery to prevent 
and treat alcohol-induced liver injury.  TNF-alpha levels in plasma and liver 
are elevated in humans and animals affected with alcoholic liver disease. In 
animal models of alcoholic liver disease, administering TNF-alpha antibodies 
attenuates liver injury and in TNF-alpha-receptor-1-deficient mice, chronic 
ethanol feeding fails to elicit liver injury. Thus, attenuation of TNF-alpha 
levels may help to ameliorate alcoholic liver disease in humans. 

Areas of Interest

Applications may focus on any one of the five general Areas of Interest 
listed below.  Proposals should include: (1) specification and rationale for 
the alcohol-related phenomena being targeted; (2) a theoretical basis and 
detailed methodology for laboratory studies; (3) a clear strategy for further 
advancing the development of promising compounds or therapies. 

Areas of research interest responsive to this announcement include, but are 
not limited to:

(1) using knowledge of receptor structures, ion channels and cellular signal 
transduction mechanisms involved in alcohol's actions on the nervous system 
to design new compounds (e.g., agonists, antagonists) for treating alcoholism 
and alcohol abuse (e.g., reducing the desire to drink, preventing withdrawal 
induced seizures). 

(2) using knowledge of the etiology of alcohol associated diseases to design 
new medications and treatments for medical conditions associated with alcohol 
abuse (e.g., fetal alcohol syndrome, liver disease, pancreatitis, 

(3) testing the potential therapeutic efficacy of existing compounds having 
known pharmacological properties (e.g., GABA receptor antagonists, 
cannibinoid antagonists, CRF antagonists) in experimental models of alcohol 
associated problems.

(4) developing new laboratory models with animal and human subjects having 
high predictive validity for specific clinical problems associated with 
alcohol abuse in humans (e.g., subjective states associated with craving, 
alcohol induced cognitive deficits).  Emphasis will be on models that can be 
used for rapid testing.

(5) conducting further basic research on the mechanisms of action of existing 
drugs and combinations of drugs currently believed to be effective in 
treating facets of alcohol abuse (e.g., naltrexone, acamprosate, SSRIs) or of 
drugs (e.g., isoflavones, CRF antagonists, CB1 antagonists, GABAa 
antagonists) demonstrated to have effects suggestive of a therapeutic effect 
(e.g., reducing alcohol consumption).  This could lead to more specific 
treatment for alcoholics with specific combination of symptoms.


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 
biomedical and behavioral research projects involving human subjects, 
unless a clear and compelling rationale and justification are 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 

All investigators proposing research involving human subjects should 
read the UPDATED "NIH Guidelines for Inclusion of Women and Minorities 
as Subjects in Clinical Research," published in the NIH Guide for 
Grants and Contracts on August 2, 2000 
(; a 
complete copy of the updated Guidelines are available at  
The revisions relate to NIH defined Phase III clinical trials and 
require: a) all applications or proposals and/or protocols to 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) all investigators to report accrual, 
and to conduct and report analyses, as appropriate, by sex/gender 
and/or racial/ethnic group differences.


It is the policy of NIH that children (i.e., individuals under the age 
of 21) must be included in all human subjects research, conducted or 
supported by the NIH, unless there are scientific and ethical reasons 
not to include them.  This policy applies to all initial (Type 1) 
applications submitted for receipt dates after October 1, 1998.

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" that was published 
in the NIH Guide for Grants and Contracts, March 6, 1998, and is 
available at the following URL address: 

Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRIES.  Program staff may also provide additional relevant 
information concerning the policy.


NIH policy requires education on the protection of human subject 
participants for all investigators submitting NIH proposals for 
research involving human subjects.  This policy announcement is found 
in the NIH Guide for Grants and Contracts Announcement dated June 5, 
2000, at the following website:

DATA AND SAFETY MONITORING PLAN (applies if you have proposed a 
clinical trial):
As of the October 2000 receipt date, applicants must supply a general 
description of the Data and Safety Monitoring Plan for ALL clinical 
trials; this must be included in the application
The degree of monitoring should be commensurate with risk. NIH Policy 
for Data and Safety Monitoring requires establishment of formal Data 
and Safety Monitoring Boards for multi-site clinical trials involving 
interventions that entail potential risk to the participants. The 
absence of this information will negatively affect your priority score.


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.  Reviewers are cautioned that their anonymity may 
be compromised when they directly access an Internet site.


The Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at:

Applicants may wish to place data collected under this RFA 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.


Prospective applicants are asked to submit a letter of intent that includes a 
descriptive title of the proposed research, the name, address, and telephone 
number of the Principal Investigator, the identities of other key personnel 
and participating institutions, and the number and title of the RFA in 
response to which the application may be submitted.  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 to:

Extramural Project Review Branch 
National Institute on Alcohol Abuse and Alcoholism 
6000 Executive Boulevard, Room 409, MSC 7003 
Bethesda, MD  20892-7003 
Rockville, MD  20852 (for express/courier service) 
Telephone:  (301) 443-4375  FAX:  (301) 443-6077 

by the letter of intent receipt date listed.


The PHS 398 research grant application instructions and forms (rev. 
5/2001) at are 
to be used in applying for these grants and will be accepted at the 
standard application deadlines ( 
as indicated in the application kit.  This version of the PHS 398 is 
available in an interactive, searchable PDF format. The NIH will return 
applications that are not submitted on the 5/2001 version.  For further 
assistance contact GrantsInfo, Telephone 301/710-0267, Email:


The modular grant concept establishes specific modules in which direct costs 
may be requested as well as a maximum level for requested budgets. Only 
limited budgetary information is required under this approach.  The 
just-in-time concept allows applicants to submit certain information only 
when there is a possibility for an award. It is anticipated that these 
changes will reduce the administrative burden for the applicants, reviewers 
and NIH staff.  The research grant application form PHS 398 (rev. 5/2001) at is to be used in 
applying for these grants, with modular budget instructions provided in 
Section C of the application instructions.

The RFA label available in the PHS 398 (rev. 5/2001) application form must be 
affixed to the bottom of the face page of the application.  Type the RFA 
number on the label.  Failure to use this label could result in delayed 
processing of the application such that it may not reach the review committee 
in time for review.  In addition, the RFA title and number must be typed on 
line 2 of the face page of the application form and the YES box must be 
marked. The RFA label is also available at:

Submit a signed, typewritten original of the application, including the 
Checklist, and three signed, photocopies, in one package to:

BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application must be 
sent to:

Chief, Extramural Project Review Branch 
National Institute on Alcohol Abuse and Alcoholism 
6000 Executive Boulevard, Suite 409, MSC 7003 
Bethesda, MD  20892-7003 Rockville, MD  20852 (for express/courier service) 

Applications must be received by the application receipt date listed in the 
heading of this RFA.  If an application is received after that date, it will 
be returned to the applicant without review.

The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  The 
CSR will not accept any application that is essentially the same as one 
already reviewed. This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must 
include an Introduction addressing the previous critique.


Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NIAAA.  Incomplete and/or non-responsive applications 
will be returned to the applicant without further consideration.

Applications that are complete and responsive to the RFA will be evaluated 
for scientific and technical merit by an appropriate peer review group 
convened by the NIAAA in accordance with the review criteria stated below.  
As part of the initial merit review, all applications will receive a written 
critique and undergo a process in which only those applications deemed to 
have the highest scientific merit, generally the top half of the applications 
under review, will be discussed, assigned a priority score, and receive a 
second level review by the National Advisory Council on Alcohol Abuse and 

Review Criteria

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.  Each 
of these criteria will be addressed and considered in assigning the overall 
score, weighting them as appropriate for each application.  Note that 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.  For 
example, an investigator may propose to carry out important work that by its 
nature is not innovative but is essential to move a field forward.

(1) Significance:  Does this study address an important problem?  If the aims 
of the application are achieved, how will scientific knowledge be advanced?  
What will be the effect of these studies on the concepts or methods that 
drive this field?

(2) Approach:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project?  Does the applicant acknowledge potential problem areas and consider 
alternative tactics?

(3) Innovation:  Does the project employ novel concepts, approaches or 
method? Are the aims original and innovative?  Does the project challenge 
existing paradigms or develop new methodologies or technologies?

(4) Investigator:  Is the investigator appropriately trained and well suited 
to carry out this work?  Is the work proposed appropriate to the experience 
level of the principal investigator and other researchers (if any)?

(5) Environment:  Does the scientific environment in which the work will be 
done contribute to the probability of success?  Do the proposed experiments 
take advantage of unique features of the scientific environment or employ 
useful collaborative arrangements?  Is there evidence of institutional 

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

o  The adequacy of plans to include both genders, minorities and their 
subgroups, and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 

o  The reasonableness of the proposed budget and duration in relation to the 
proposed research.

o  The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project  
proposed in the application.


Letter of Intent Receipt Date:    December 28, 2001
Application Receipt Date:         January 23, 2002
Peer Review Date:                 March-April 2002
Council Review:                   May 2002
Earliest Anticipated Start Date:  July 1, 2002


Award criteria that will be used to make award decisions include:

o  scientific merit (as determined by peer review)
o  availability of funds
o  programmatic priorities.


Inquiries concerning this RFA are encouraged.  The opportunity to clarify any 
issues or answer questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Mark Egli, Ph.D.
Division of Basic Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 402
Bethesda, MD  20892-7003 [for express mail, use Rockville, MD  20852]
Tel:  (301) 594-6382	
FAX:   (301) 594-0673

Direct inquiries regarding fiscal matters to:

Judy Fox Simons
Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism
Willco Building, Suite 505
6000 executive Blvd. (MSC-7003)
Bethesda, MD  20892-7003
(For express mail use:
Rockville, MD  20852)
Telephone:  (301) 443-2434


This program is described in the Catalog of Federal Domestic Assistance No. 
93.273.  Awards are made under authorization of Sections 301 and 405 of the 
Public Health Service Act as amended (42 USC 241 and 284) and administered 
under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 
74 and 92.  This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and promote the non-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.

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