NEUROBIOLOGICAL EFFECTS OF DRUG ADDICTION THERAPIES

NIH GUIDE, Volume 26, Number 40, December 19, 1997

RFA NUMBER:  DA-98-004

P.T.

National Institute on Drug Abuse

Letter of Intent Receipt Date:  February 26, 1998
Application Receipt Date:  March 26, 1998

PURPOSE

This Request for Applications (RFA) solicits research grant applications that
investigate the effects of behavioral and/or pharmacological drug addiction
therapies on structure and/or function of the human central nervous system. 
Through the use of clinical neurobiological approaches, such as neuroimaging,
considerable information is now being amassed that reveals how drugs of abuse
and addiction alter brain processes.  However, a critical question that
remains to be addressed is how drug addiction therapies (whether behavioral,
pharmacological, or both) might affect altered brain structure and/or
function.  For example, do drug addiction therapies "reset" or "normalize"
brain biology and/or chemistry altered by chronic drug exposure?  Results from
such studies could provide vital insights for the development and improvement
of behavioral and medication treatment of patients with drug use disorders.

This research program is intended to support individual research project
grants, mentored career development awards, and competitive supplements on the
clinical neurobiological effects of specific treatments for drug use
disorders.  Research using animals (particularly primates) is not excluded,
but any animal research submitted under this RFA must serve an essential, but
secondary role, in a predominantly clinical study.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of "Healthy People 2000" a PHS-led national
activity for setting priority areas.  This Request for Applications (RFA),
Neurobiological Effects of Drug Addiction Therapies, is related to the
priority area of alcohol and other drugs.  Potential applicants may obtain a
copy of "Healthy People 2000" (Full Report:  Stock No. 017-001-00474-0 or
Summary Report:  Stock No. 017-001-00473-1) through the Superintendent of
Documents, Government Printing Office, Washington, DC 20402-9325 (telephone
(202) 512-1800).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by foreign and domestic, for-profit and
nonprofit organizations, public and private; such as, colleges, universities,
hospitals, laboratories, units of State and local government, and eligible
agencies of the Federal Government.  Racial/ethnic minority individuals, women
and persons with disabilities are encouraged to apply as Principal
Investigators.  Foreign institutions are not eligible for career development
(K-series) awards.  Awards to foreign institutions under other research (R-
series) mechanisms are generally limited to 3 years.

MECHANISM OF SUPPORT

Research support mechanisms include the National Institutes of Health (NIH)
research project grants (R01), exploratory/ developmental grant (R21), and
small grant (R03), as well as Mentored Research Scientist Development (K01)
and Mentored Clinical Scientist Development (K08) Awards.  In addition,
competitive supplements to add a research component to an existing grant will
be eligible.

The total project period for an application submitted in response to this RFA
may not exceed five years.  The anticipated award date is December 30, 1998. 
This RFA is a one-time solicitation. Future unsolicited competitive supplement
applications will compete with all investigator-initiated applications and be
reviewed according to standard  peer review procedures. Applications judged to
be non-responsive to the RFA will be returned to the applicant.

The exploratory/developmental (R21) applications are limited to 3 years and
small grant (R03) applications are limited to 2 years, non-renewable, and
limited in direct cost amount per year (R03, $50,000; R21, $90,000).  The R03
mechanism is intended for newer, less experienced investigators, for
investigators at institutions without a research tradition, or for experienced
investigators wishing to change research directions or test new methods or
techniques.  The R21 mechanism is intended to encourage exploratory research
projects with sound methodology and strong rationales in underdeveloped
research areas of drug abuse. Mentored Research Scientist Development Award
(K01) and Mentored Clinical Scientist Development Award (K08) mechanisms are
intended to provide a period of sponsored research experience that will then
enable the applicant to pursue an independent research career.  The K01 and
K08 awards support 3-5 years of mentored research experience, and applicants
are required to devote at least 75% time to the program.  K01 Awards require a
research or a health-professional doctorate or equivalent, while K08 Awards
require a clinical degree or equivalent.  There are additional special
requirements for these mechanisms; if any applicant intends to apply for
either award under this RFA, he or she should contact the program official
listed under the INQUIRIES section for further information.  Specific
information on individual research mechanisms can be obtained from the NIDA
homepage at: www.nida.nih.gov/Funding.html.

The competitive supplements will be reviewed in accordance with NIH standard
review procedures; i.e., peer review/Council review. Competitive supplement
requests are to be submitted on the RFA receipt date.

All applications submitted in response to this RFA should use the Just-In-Time
(JIT) submission procedures.  These procedures were published in the NIH
Guide, Volume 25, Number 10, March 29, 1996, with additional instructions
published in Volume 25, Number 16, May 17, 1996.  Copies of these two Guide
publications are available from the contact person listed under INQUIRIES or
on the NIH (http://www.nih.gov) or NIDA (http://www.nida.nih.gov) home pages.

FUNDS AVAILABLE

In FY 1998, it is anticipated that 12 to 14 awards may be funded at a total
cost of $2 million, and of that amount approximately $500,000 will be
available for competitive supplements.  Funding of approximately 7 research
grant (R01) awards at an average grant award of $200,000 (total cost) is
anticipated, as well as funding of 5 to 7 other award mechanisms of support
listed in this RFA. It is anticipated NIDA will reissue this RFA again in FY
1999, subject to availability of funds.

Because the nature and scope of the research proposed in response to this RFA
may vary, the size of an award will vary also.

RESEARCH OBJECTIVES

Recent advances in clinical neurobiological methods have armed researchers
with a powerful set of approaches to investigate how drugs of abuse affect the
brain.  However, little is known about how these alterations may be influenced
by abstinence or treatment.  The principal goal of the research to be
supported through this initiative is to identify how structure and/or function
of neuronal systems are affected by specific treatments for drug use
disorders.  Toward this goal, NIDA is particularly interested in proposals
that will utilize brain imaging and/or other state-of-the-art approaches for
assessment of alterations in human brain function and structure during and
following behavioral and/or pharmacological therapy for drug disorders.  The
following specific research questions serve only as a guide to the types of
research areas that are encouraged in this RFA and are not meant to be all
inclusive:

-  Chronic use of drugs can lead to compulsive drug-seeking behavior. Results
in both animals and humans have shown that drugs of abuse alter
neurobiological and neurochemical systems.  The "addicted" brain is one than
is functionally and structurally altered. Clinical neurobiological studies
which would reveal how drug addiction therapies serve to "reset" or
"normalize" this altered brain state are needed.

-  Both pharmacological and behavioral treatments have been shown to be
effective, and clinically significant interactions between these modalities
have been demonstrated.  Very little is known, however, about the mechanisms
underlying these interactions. Therefore, studies neurobiologically
characterizing the mechanistic commonalities and differences between these
treatment modalities are encouraged, as are studies that elucidate the
neurobiological basis of interactions between combined treatments.

-  Important relationships between substance use disorders and comorbid
neuropsychiatric disorders have been described, but the mechanisms underlying
these relationships and their implications for drug addiction treatment remain
poorly understood.  Investigators are encouraged to elucidate the specific
neurobiological relationships and to determine their implications of drug
addiction treatment.

-  Concurrent use of multiple drugs of abuse poses a serious and frequent
clinical challenge.  NIDA encourages studies aimed at neurobiological
detection and characterization of differences in treatment response between
single- and polydrug abusers.

-  Similarly, studies that will detect and characterize neurobiological
markers predictive of  treatment efficacy are also of interest.

-  As research has shown sex/gender differences in the neurobiological
response to abused drugs and in the pharmacologic treatment of drug abuse, it
is strongly advised that studies include sex/gender analyses.  Also, studies
assessing ethnicity or HIV/AIDS status-differences in neurobiological effects
of treatment are particularly welcome.

All applications must address issues of project feasibility, implementation of
the study, study design, sampling procedure, instrumentation and measurement,
data collection, tracking of subjects, follow up, and data analysis, as
appropriate.

Investigators are encouraged to offer HIV testing and counseling in accordance
with current guidelines to subjects identified during the course of the
research as at risk for HIV acquisition or transmission.

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 subpopulations 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 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
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research," which were published in the Federal Register on March 28, 1994 (FR
59 14508-14513) and in the NIH Guide for Grants and Contracts, Volume 23,
Number 11, March 18, 1994.  Investigators also may obtain copies of the policy
from the program staff listed under INQUIRIES. Program staff may also provide
additional relevant information concerning the policy.

NATIONAL ADVISORY COUNCIL ON DRUG ABUSE RECOMMENDED GUIDELINES FOR THE
ADMINISTRATION OF DRUGS TO HUMAN SUBJECTS

The National Advisory Council on Drug Abuse recognizes the importance of
research involving the administration of drugs to human subjects and has
developed guidelines relevant to such research.  Potential applicants are
encouraged to obtain and review these recommendations before submitting an
application that will administer compounds to human subjects.  The guidelines
are available on NIDA's Home Page at http://www.nida.nih.gov under What's New
or may be obtained by calling (301) 443-2755.

LETTER OF INTENT

Prospective applicants are asked to submit, by February 26, 1998, 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 is being 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 NIDA staff to estimate the potential review workload and avoid conflict
of interest in the review.

The letter of intent is to be sent to:

Director, Office of Extramural Program Review
National Institute on Drug Abuse
5600 Fishers Lane, Room 10-42
Rockville, MD  20857
Telephone:  (301) 443-2755
FAX:  (301) 443-0538

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS 398 (rev.
5/95).  Application kits are available at most institutional offices of
sponsored research and may be obtained from the Division of Extramural
Outreach & Information Resources, National Institutes of Health, 6701
Rockledge Drive, Room 3034, MSC 7762, Bethesda, MD 20892-7762, telephone (301)
710-0267, Email asknih@od.nih.gov.

The RFA label available in the PHS 398 (rev. 5/95) application form must be
affixed to the bottom of the face page of the application.  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 Item 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 three signed, photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW (formerly Division of Research Grants)
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for courier/overnight mail service)

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

Director, Office of Extramural Program Review
National Institute on Drug Abuse
5600 Fishers Lane, Room 10-42
Rockville, MD  20857

Applications must be received by March 26, 1998.  If an application is
received after that date, it will be returned to the applicant without review. 
The Center for Scientific Research (CSR) will not accept any application in
response to this RFA that is essentially the same as one currently pending
initial review. This does not preclude the submission of substantial revisions
of applications already reviewed, but such applications must include an
introduction addressing the previous critique.

Schedule:

Letter of Intent Receipt Date:  February 26, 1998
Application Receipt Date:       March 26, 1998
Peer Review Date:               June/July 1998
Council Review:                 September 1998
Earliest Start Date:            September 30, 1998

REVIEW CONSIDERATIONS

Applications that are complete will be evaluated for scientific and technical
merit by an appropriate peer review group convened by the NIDA in accordance
with 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
council or board.  Small grant applications do not receive a second-level
Council review.

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 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.

The above criteria apply to R01 applications, and there are additional
criteria for other mechanisms.  When applying under other mechanisms, the
applicants should obtain a copy of the relevant announcement from either their
office of sponsored research, Grants Management Branch at NIDA (301-443-6710),
or NIDA's homepage (www.nida.nih.gov).  These announcements contain
instructions for the preparation of grant applications that must be strictly
adhered to and describe review criteria that will be used by a peer review
committee in evaluating submitted applications.  In addition to the above-
mentioned criteria, relevance of the application to the goal and objectives of
this RFA will also be an important consideration.

AWARD CRITERIA

Award criteria that will be used to make award decisions include: scientific
merit (as determined by peer review), availability of funds, and programmatic
priorities.

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Arthur MacNeill Horton, Jr., Ed.D.
National Institute on Drug Abuse
5600 Fishers Lane, Room 10A-46
Rockville, MD  20857
Telephone:  (301) 443-4877
FAX:  (301) 443-6814
Email:  ah61x@nih.gov

Direct inquiries regarding fiscal matters to:

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse
5600 Fishers Lane, Room 8A-54
Rockville, MD  20857
Telephone:  (301) 443-6710
Email:  gf6s@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.279.  Awards are made under authorization of the Public Health Service Act,
Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC
241 and 285), and administered under PHS grants policies and Federal
Regulations 42 CFR 52 and 45 CFR Part 74.  This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review.

The Public Health Service (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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