This Program Announcement expires on October 5, 2004, unless renewed.

MECHANISMS OF ACTION OF BEHAVIORAL TREATMENTS FOR ALCOHOLISM

Release Date:  October 4, 2001

PA NUMBER:  PA-02-007

National Institute on Alcohol Abuse and Alcoholism (NIAAA)
 (http://www.niaaa.nih.gov/)

THIS PA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  MODULAR 
INSTRUCTIONS MUST BE USED FOR RESEARCH GRANT APPLICATIONS UP TO $250,000 PER 
YEAR. MODULAR BUDGET INSTRUCTIONS ARE PROVIDED IN SECTION C OF THE PHS 398 
(REVISION 5/2001) AVAILABLE AT 
http://grants.nih.gov/grants/funding/phs398/phs398.html.

PURPOSE

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is seeking 
research grant applications on the mechanisms of action of treatments for 
alcoholism.  Although advances have been made in the behavioral and 
pharmacological interventions for alcoholism treatment, limited information is 
known about how, why, and when these treatments are effective.  Understanding 
the mechanisms of action of an intervention involves identifying the active 
processes and/or components of treatments and how they result in positive 
outcomes.  Various research topics that need to be investigated include 
identification and evaluation of factors that mediate and moderate treatment 
efficacy, elucidation of causal chains underlying treatment effects, 
clarification of the additive and subtractive effects of complex therapies, 
and identification of the biological basis underlying the effectiveness of 
therapies.  These studies of mechanisms can be conducted within the context of 
efficacy trials or other treatment evaluation designs. 

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 Program Announcement (PA) 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/.

ELIGIBILITY REQUIREMENTS

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.  Faith-based organizations are eligible to 
apply for these grants.  Racial/ethnic minority individuals, women, and 
persons with disabilities are encouraged to apply as principal investigators.

MECHANISM OF SUPPORT

This PA 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.  The total 
project period for an application submitted in response to this PA may not 
exceed five (5) years.  Facilities and Administrative (F&A) costs will be 
awarded based on the negotiated rate at the time of the award.  More detailed 
information on the R21 mechanism can be found at 
http://grants.nih.gov/grants/guide/pa-files/PA-99-131.html. 

Applications requesting direct costs of $500,000 or more in any one year must 
obtain written agreement from the NIAAA that the application will be accepted 
for consideration of award, in accordance with NIH policy, which is available 
at http://grants.nih.gov/grants/guide/notice-files/not98-030.html. 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 cannot be renewed: however, a no-cost 
extension of up to one year may be granted prior to expiration of the project 
period.  Investigators are encouraged to seek continued support after 
completing an exploratory/developmental grant project through a research 
project grant (R01).

Specific application instructions have been modified to reflect "MODULAR 
GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH. 
Complete and detailed instructions and information on Modular Grant 
applications can be found at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

RESEARCH OBJECTIVES

During the past decade advances have been made in behavioral and 
pharmacological interventions for alcoholism treatment.  These interventions 
include motivational enhancement therapy, brief interventions, behavioral 
couples therapy, twelve-step facilitation therapy, community reinforcement 
approach, and medications such as naltrexone and acamprosate.  Although these 
interventions are effective in reducing or preventing drinking, limited 
information is known about how and why these treatments are effective.  
Understanding the mechanisms of action of an intervention involves identifying 
the active processes and/or components of treatments and how they result in 
positive outcomes.  This knowledge is important not merely for theoretical 
reasons, but so that interventions can be made more effective for the greatest 
numbers of patients under diverse conditions.  Specification of the critical 
active components of treatments might allow existing interventions to be 
modified in a manner which enhances these components as well as modifying or 
eliminating the ingredients of the treatment that yield less positive effects. 
Further, understanding efficacy elements across alcohol interventions may 
facilitate development of new treatments with greater efficacy than existing 
ones. In light of the importance of this topic, the NIAAA Advisory Council 
Subcommittee in its 1999 Review of the Extramural Research Portfolio for 
treatment strongly recommended this area as their first priority.  

Research on mechanisms is broad in nature and in many instances, might be 
integrated meaningfully and economically into existing research projects.  In 
other instances, separate confirmatory studies may be required.  Contributions 
of possible active components from biological, psychological, behavioral, 
social, environmental and spiritual perspectives are encouraged.  Finally, 
components may relate to the nature of the treatment itself, characteristics 
of the patient, provider characteristics, or features of the patient-provider 
interaction.  Both existing, validated treatments, and new treatments may be 
studied, as well as phenomena surrounding natural recovery. 

Several research topics are proposed to investigate the mechanisms of 
treatments include but are not limited to:  

- Identify and evaluate factors that mediate and moderate treatment efficacy.  
These include treatment, patient, and environmental variables. The 
contribution of individual components as well as the relative contribution of 
active components and their interactions with biological, social, 
environmental, and spiritual perspectives should be considered.  Treatment 
variables include components, structure, process, counselor characteristics, 
and features of the patient-provider interaction. Patient variables consist of 
motivation, family history, developmental state, commitment to goals of 
treatment, coping skills, comorbidities, and expectancies.  Environmental and 
social supports include family and friends. 

- Elucidate causal chains underlying treatment effects.  Causal chain analyses 
specify and test the sequence of steps (or pathway) leading from the 
intervention to the final outcome, and are often built around mediator and 
moderator effects.  This series of linked events can be evaluated 
statistically to support or reject a hypothesized model of therapy.  A 
classification of types of causal chains and the analytic methods required to 
test them have been drawn from other disciplines and applied to alcoholism 
treatment.  This work provides a solid base for more systematic inclusion of 
causal chain analyses in treatment research studies.

- Clarify the additive and subtractive effects of complex therapies.  
Therapies are complex, often composed of distinct, but interrelated 
components, and become increasingly more complex in the case of combined 
treatments and stepped-care algorithms.  Studies designed to dismantle 
therapies, i.e., clarify their additive and subtractive effects, are needed to 
clearly identify their active components.

- Identify the biological basis underlying the effectiveness of therapies.  
The mechanism of action of therapies might be associated with changes in the 
activities of various neurotransmitters, neuromodulators, and neurohormones.  
Imaging studies before and after treatment may assist in clarifying the 
biological base for successful outcome with both behavioral and 
pharmacological therapies.  Recent developments in dynamic imaging techniques 
and advances in understanding the brain substructures involved in drinking 
have made it feasible to introduce these components into treatment evaluation 
studies.  Questions that might be addressed include: Are the same circuits 
activated in the brain that correspond to alcohol craving and to memory and 
learning associated with initiation and maintenance of drinking behavior?  Do 
behavioral therapies alter these neurocircuits?  What are the bases for 
actions of medications such as naltrexone and acamprosate?  Is there overlap 
between behavioral therapies and medications in the activation or inhibition 
of these neurocircuits?  

- Determine mechanisms of action of the placebo effect.  Attention has 
recently been focused on the “placebo effect” as a potential contributor to 
successful treatment and is currently the subject of a trans-NIH initiative.  
Studies are needed to better understand this potentially important component 
of alcohol recovery efforts.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

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 103-43). 

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 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html); 
a complete copy of the updated Guidelines are available at  
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm:  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.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

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: http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

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.

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 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: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

DATA AND SAFETY MONITORING PLAN

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 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html). 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.

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

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT

The Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide 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:
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA 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.

APPLICATION PROCEDURES

The PHS 398 research grant application instructions and forms (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html are to be used in 
applying for these grants and will be accepted at the standard application 
deadlines (http://grants.nih.gov/grants/dates.htm) as indicated in the 
application kit.  This version of the PHS 398 is available in an interactive 
format. Although applicants are encouraged to begin using the 5/2001 revision 
of the PHS 398 as soon as possible, the NIH will continue to accept 
applications prepared using the 4/1998 revision until January 9, 2002. 
Beginning January 10, 2002, however, the NIH will return applications that are 
not submitted on the 5/2001 version.  For further assistance contact 
GrantsInfo, Telephone 301/435-0714, Email: GrantsInfo@nih.gov.

Applicants planning to submit an investigator-initiated new (type 1), 
competing continuation (type 2), competing supplement, or any amended/revised 
version of the preceding grant application types requesting $500,000 or more 
in direct costs for any year are advised that he or she must contact the 
Institute or Center (IC) program staff before submitting the application, 
i.e., as plans for the study are being developed.  Furthermore, the 
application must obtain agreement from the IC staff that the IC will accept 
the application for consideration for award.  Finally, the applicant must 
identify, in a cover letter sent with the application, the staff member and 
Institute or Center who agreed to accept assignment of the application.

This policy requires an applicant to obtain agreement for acceptance of the 
original application as well as any subsequent revisions.  Refer to the NIH 
Guide for Grants and Contracts, March 20, 1998 at 
http://grants.nih.gov/grants/guide/notice-files/not98-030.html. 

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS

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
http://grants.nih.gov/grants/funding/phs398/phs398.html is to be used in 
applying for these grants, with modular budget instructions provided in 
Section C of the application instructions.  Applicants are permitted, however, 
to use the 4/1998 revision of the PHS 398 for scheduled application receipt 
dates until January 9, 2002.  If you are preparing an application using the 
4/1998 version, please refer to the step-by-step instructions for Modular 
Grants available at http://grants.nih.gov/grants/funding/modular/modular.htm.  
Additional information about Modular Grants is also available on this site.

The title and number of the program announcement must be typed on line 2 of 
the face page of the application form and the YES box must be marked.

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

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

REVIEW CONSIDERATIONS

Applications will be assigned on the basis of established PHS referral 
guidelines.  Applications will be evaluated for scientific and technical merit 
by an appropriate scientific review group convened in accordance with the 
standard NIH peer review procedures.  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 applications under review, will be discussed, assigned a 
priority score, and receive a second level review by the appropriate national 
advisory council or board.

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 
support?

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 
evaluated.

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.

o  The adequacy of the proposed plan to share data, if appropriate.


AWARD CRITERIA

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

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

Direct inquiries regarding programmatic issues to:

Margaret E. Mattson, Ph.D.
Division of Clinical and Prevention Research
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) 443-0796
FAX:  (301)443-8774
Email:  mmattson@willco.niaaa.nih.gov

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
Email:  jsimons@willco.niaaa.nih.gov

AUTHORITY AND REGULATIONS 

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 and contract 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, and 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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