From: kristoff@NET.BIO.NET (Dave Kristofferson)
Newsgroups: bionet.sci-resources
Subject: NIH Guide, vol. 21, no. 42, pt. 3, 20 November 1992
Date: 21 Nov 92 04:20:51 GMT
Distribution: bionet


$$XID RFA HL9305 HL-93-05 P1O1 *****************************************

EFFECTS OF SEX HORMONES ON CORONARY ARTERY REACTIVITY

NIH GUIDE, Volume 21, Number 42, November 20, 1992

RFA:  HL-93-05-H

P.T. 34; K.W. 0715040, 0760025, 0760085, 1002061, 0765035

National Heart, Lung, and Blood Institute

Letter of Intent Receipt Date:  February 1, 1993
Application Receipt Date:  April 27, 1993

PURPOSE

The Division of Heart and Vascular Diseases invites grant applications
for up to five years of support for research into the roles of sex
hormones in the physiology and pathophysiology of the coronary
vasculature.  The ultimate goal is to develop insights into therapeutic
approaches for reducing the higher incidence of coronary diseases in
men and post-menopausal women than pre-menopausal women.

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), Effects of Sex Hormones on Coronary Artery
Reactivity, is related to the priority area of heart disease and
stroke. 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 202-783-3238).

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.
Applications from minority individuals and women are encouraged.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) individual
research grant (R01). Responsibility for the planning, direction, and
execution of the proposed project will be solely that of the applicant.
The total project period for applications submitted in response to the
present RFA may not exceed five years.  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.

FUNDS AVAILABLE

Approximately $1.5 million in total cost will be provided for the first
year of support for the entire program.  It is anticipated that six new
grants will be awarded under this program.  This level of support is
dependent on the receipt of a sufficient number of applications of high
scientific merit.  Although this program is provided for in the
financial plan of the National Heart, Lung, and Blood Institute
(NHLBI), awards pursuant to this RFA are contingent upon the
availability of funds for this purpose.  Administrative adjustments in
project period and/or amount of support may be required at the time of
the award.  Since a variety of approaches would represent valid
responses to this announcement, it is anticipated that there will be a
range of costs among individual grants awarded.

RESEARCH OBJECTIVES

Background

Recent studies reveal that temporary ischemia can occur, not only as a
result of organic obstruction of the coronary artery, but also as a
result of vasoconstriction and vasospasm.  There is evidence that in
many blood vessels, the endothelium as well as the vascular smooth
muscle plays an active role in the control of vascular reactivity.  The
regulation of vascular reactivity, especially in the coronary arteries,
may have a significant effect on vasospasm and the development of
coronary vascular disease.

Gender is one of the major risk factors for the development of coronary
artery disease.  Epidemiological studies show that young men are at
higher risk than young women and that this prominent difference
decreases in post-menopausal women.  Involvement of sex hormones in
vascular reactivity has been suggested frequently but clear evidence
for a mechanism is lacking.  Gender differences in vascular reactivity
have been demonstrated by several research groups which suggest that
the function of the endothelium and vascular smooth muscle are sexually
differentiated and modulated by sex hormones.  In these studies, a
number of vessel segments from female and male animals treated with
estrogen relaxed significantly more in response to both
endothelium-dependent and endothelium-independent vasodilators than did
ring segments from male or female animals treated with testosterone.
In other studies, the tension generated by the vascular smooth muscle
in response to the vasoconstrictors was greater in aortas from male
than female rats.  Moreover, removal of the endothelium and treatment
with testosterone increases the responsiveness of the aorta of female
rats.  These observations suggest that the endothelium of male rats has
a lesser capacity to inhibit contractions of the underlying vascular
smooth muscle, possibly because it releases less endothelium-dependent
relaxation factors under basal conditions.  The expression of gender
differences in vascular responses, however, depends on the vessel
itself.  Although several studies have demonstrated that coronary
vessels from male animals show greater vascular reactivity, the degree
to which coronary smooth muscle and the endothelium are sexually
differentiated and modulated by sex hormones remains to be determined.

It has been suggested that one of the protective effects of estrogens
may be mediated through several systemic and local processes which
include the direct and indirect effects of estrogens on structural
elements of the vessel wall.  Limited but significant data have
identified the presence of androgen, progesterone and estrogen
receptors in the coronary vasculature in experimental animals and
progesterone receptors have been identified in coronary arteries of
men.  However, no attempt has been made to see whether there is a sex
difference in the distribution and density of steroid binding sites.
These results can only be viewed as qualitative information regarding
the existence of hormone-specific target cells.  In fact,
identification of steroid hormone receptors in a potential target
tissue does not necessarily establish physiological function.  Receptor
concentration is influenced by hormonal stimulation, sex, maturation,
aging, and probably many other factors.  These variations should be
taken into consideration while evaluating the effects of sex hormones
on the coronary vasculature.  While recent studies have suggested that
androgen and estrogen may modulate specific functions of aortic smooth
muscle cells and that elevations in circulating concentrations of
endogenous estrogen may influence the function of vascular endothelial
or smooth muscle cells of the coronary artery, a correlation between
steroid hormone receptors and hormonal modulation of cell function in
the coronary vasculature still needs to be determined.  Also, the role
of the coronary reactivity should be evaluated in mature and immature
animals of both sexes in terms of its morphological, pharmacological,
and biophysiochemical characteristics.

Sex hormones interact with the sympathetic nervous system at the
peripheral level.  Testosterone and estrogen have been shown to inhibit
norepinephrine uptake and inactivation in isolated hearts of rats.
Also, gender differences have been described in the distribution of
endogenous catecholamines and in alpha receptor affinity.  These data
suggest that sympathetic control of the vascular reactivity exhibits a
dimorphic pattern due to the action of sex hormones.  The coronary
circulation is predominately regulated by the sympathetic nervous
system.  Physiological stress such as exercise and hypoxia increases
the sympathetic activity of the heart.  Whether or not the coronary
vascular bed responds to these stimuli in a sexually differentiated
manner is still unclear.  The evaluation of the interaction between the
sympathetic mechanism and the sex hormones in this specific vascular
bed will certainly provide important information regarding the
mechanisms underlying coronary vascular disease under normal and
stressful conditions in men and women across all ages.

Objectives and Scope

All applications must be focussed on the role of the sex hormones on
coronary reactivity.  The spectrum of experimental approaches
considered responsive to this RFA includes in vivo and ex vivo studies
of coronary vascular reactivity, co-culture techniques to elucidate
cell to cell interaction, cell receptor density, as well as molecular
pharmacological approaches that will enhance our understanding of how
sex hormones regulate coronary vascular cell function.

Proposed Research

Examples of research projects are given below, however, these are
provided for illustrative purposes only.  Applicants may consider other
projects that may contribute to the goals of this initiative, but are
not included in this list.

o  Identification of the distribution and density of sex hormone
receptors on the coronary vessels under different sex-, age- and
cycle-related conditions.

o  Evaluation of the correlation between sex hormone receptors and
hormonal modulation of cell function.

o  Differentiation between acute and chronic effects of sex hormones on
coronary reactivity.

o  Evaluation of the expression of sexual dimorphism in coronary
vascular reactivity which is controlled by the sympathetic nervous
system under different physiological conditions.

o  Identification of the cellular and molecular mechanisms modulated by
sex hormones.

SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS

NIH policy is that applicants for NIH clinical research grants and
cooperative agreements will be required to include minorities and women
on study populations so that research findings can be of benefit to all
persons at risk of the disease, disorder or condition under study;
special emphasis should be placed on the need for inclusion of
minorities and women in studies of diseases, disorders and conditions
which disproportionately affect them.  This policy is intended to apply
to males and females of all ages.  If women or minorities are excluded
or inadequately represented in clinical research, particularly in
proposed-population based studies, a clear compelling rationale must be
provided.

The composition of the proposed study population must be described in
terms of gender.  In addition issues of gender should be addressed in
developing a research design and sample size appropriate for the
scientific objectives of the study.  This information should be
included in the form PHS 398 in Sections 1-4 of the research plan AND
summarized in Section 5, Human Subjects.  Applicants are urged to
assess carefully the feasibility of including adequate numbers of
women.

For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and prevention strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but not limited to clinical trials.

The usual NIH policies concerning research on human subjects also
apply.  Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded.  However,
every effort should be made to include human tissues from women when it
is important to apply the results of the study broadly, and this should
be addressed by applicants.

For foreign awards, the policy on inclusion of women applies fully;
since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States' populations, including
minorities.

If the required information is not contained within the application,
the application will not be accepted for review.

Peer reviewers will address specifically whether the research plan in
the application conforms to these policies.  If the representation of
women is inadequate to answer the scientific question(s) addressed AND
the justification for the selected study population is inadequate, it
will be considered a scientific weakness or deficiency in the study
design and will be reflected in assigning the priority score to the
application.

All applications for clinical research submitted to NIH are required to
address these policies. NIH funding components will not award grants or
cooperative agreements that do not comply with these policies.

LETTER OF INTENT

Prospective applicants are asked to submit, by February 1, 1993, 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 subsequent applications, the information
that it contains is helpful in planning for the review of applications.
It allows NHLBI staff to estimate the potential review workload and to
avoid conflict of interest in the review.

The letter of intent is to be sent to:

Review Branch
Chief, Centers and Special Projects Section
Division of Extramural Affairs
National Heart, Lung and Blood Institute
Westwood Building, Room 553A
Bethesda, MD  20892

APPLICATION PROCEDURES

The research grant application for PHS 398 (rev. 9/91) is to be used in
applying for these grants.  These forms are available at most
institutional offices of sponsored research and may be obtained from
the Office of Grants Inquiries, Division of Research Grants, National
Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892,
telephone 301-496-7441.

The RFA label available in the PHS 398 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,
to identify the application as a response to this RFA, Check "YES",
enter the title "Effects of Sex Hormones on Coronary Artery
Reactivity", and the RFA number HL-93-05-H on Line 2a of the face page
of the application.

Send or deliver a signed, typewritten original of the application,
including the checklist, and three signed photocopies to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

Send two additional copies of the application to the Chief Centers and
Special Projects Section, at the address listed under LETTER OF INTENT.
It is important to send these two copies at the same time as the
original and three copies are sent to the Division of Research Grants
(DRG).  Otherwise, the NHLBI cannot guarantee that the application will
be reviewed in competition for this RFA.

Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research Resources
may wish to identify the GCRC as a resource for conducting the proposed
research.  If so, a letter of agreement from either the GCRC program
director or principal investigator could be included with the
application.

Applications must be received by April 27, 1993. If an application is
received after that date, it will be returned to the applicant without
review.  The DRG will not accept any application in response to this
announcement that is essentially the same as one currently pending
initial review, unless the applicant withdraws the pending application.
The DRG 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 initiation of the program, the Division of Heart and Vascular
Diseases will sponsor periodic meetings to encourage exchange of
information among investigators who participate in this program, and to
stimulate collaboration.  Applicants should request additional travel
funds for a one-day meeting each year, most likely to be held in
Bethesda, Maryland.  Applicants should also include a statement in
their applications indicating their willingness to participate in these
meetings.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed by NIH staff for
completeness and responsiveness. Incomplete applications will be
returned to the applicant without further consideration.  If the
application is not responsive to the RFA, NHLBI staff will contact the
applicant to determine whether to return the application to the
applicant or submit it for review in competition with unsolicited
applications at the next review cycle.

Applications may be triaged by an NHLBI peer review group on the basis
of relative competitiveness.  The NIH will withdraw from further
competition those applications judged to be non-competitive for award
and notify the applicant Principal Investigator and institutional
official.  Those applications judged to be competitive will undergo
further scientific merit review.  Those applications that are complete
and responsive will be evaluated in accordance with the criteria stated
below for scientific/technical merit by an appropriate peer review
group convened by the NHLBI.  The second level of review will be
provided by the National Heart, Lung, Blood Advisory Council.

Review criteria for RFAs are generally the same as those for
unsolicited research grant applications.

o  the novelty, originality and feasibility of the approach and the
adequacy of the experimental design

o  the competence of the principal investigator and collaborators to
accomplish the proposed research, and the commitment and time they will
devote to the project

o  the suitability of the facilities to perform the proposed research,
including laboratories, instrumentation and data management systems

o  the appropriateness of the requested budget and duration for the
proposed research

o  adequate plans for interaction and communication of information and
concepts among investigators involved in collaborative studies

AWARD CRITERIA

Although multidisciplinary approaches are encouraged, it is not the
intent of this announcement to solicit applications for large studies
that would encompass a variety of independent project, i.e., program
projects.  This program will not support clinical trials or large
epidemiological studies.  In general, funds will not be provided for
the purchase and installation of expensive, new equipment.  Awards
under this announcement to foreign institutions will be made only for
research of very unusual merit, need and promise, and in accordance
with Public Health Service policy governing such awards.

The anticipated date of award is December 1, 1993.

INQUIRIES

Inquiries regarding this announcement may be directed to:

Dr. Isabella Liang
Cardiac Diseases Branch
Division of Heart and Vascular Diseases
National Heart, Lung and Blood Institute
Federal Building, Room 3C06
Bethesda, MD  20892
Telephone:  (301) 496-1081
FAX:  (301) 480-6282

Direct inquiries regarding fiscal and administrative matters to:

Mr. William Darby
Grants Operations Branch
Division of Extramural Affairs
National Heart, Lung and Blood Institute
Westwood Building, Room 4A11
Bethesda, MD  20892
Telephone:  (301) 496-7536
FAX:  (301) 402-1200

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance
No. 93.837, Heart and Vascular Diseases.  Awards will be made under the
authority of the Public Health Service Act, Section 301 (42 USC 241)
and administered under PHS grants policies and Federal regulations,
most specifically 42 CFR Part 52 and 45 CFR Part 74.  This program is
not subject to the Intergovernmental review requirements of Executive
Order 12372, or to Health Systems Agency Review.


$$XID RFA PA9321 PA-93-21 P1O1 *****************************************

DRUG ABUSE TREATMENT OF CRIMINAL JUSTICE-INVOLVED POPULATIONS

NIH GUIDE, Volume 21, Number 42, November 20, 1992

PA NUMBER:  PA-93-21

P.T. 34; K.W. 0404009, 0404000, 0403004

National Institute on Drug Abuse

PURPOSE

The purpose of this announcement is to encourage research on models of
intervention for drug abusers involved with the criminal justice system
(CJS).  Applications may focus on drug abuse treatment linked to the
criminal justice system that is delivered prior to or in lieu of
incarceration, during the period of incarceration, after release, or in
combinations of these.  Applications are also sought for
community-based outreach/intervention behavioral change strategies in
the population of criminal-justice-involved drug users not in
treatment.

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 program
announcement (PA), Drug Abuse Treatment of Criminal Justice-Involved
Populations, is related to the priority area of alcohol and other
drugs.  Some applications under this announcement may also be related
to the priority area of violent and abusive behavior.  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 202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by foreign and domestic, for-profit and
non-profit, public and private organizations such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.  Women
and minority investigators are encouraged to apply.  Applications are
especially encouraged from State and municipal governments with
research units and/or State and municipal governments collaborating
with university-based research units.

MECHANISM OF SUPPORT

This program announcement will use the National Institutes of Health
(NIH) individual research grant (R01).  Responsibility for the
planning, direction, and execution of the proposed project will be
solely that of the applicant.  Support will be provided for a period of
up to five years (renewable for subsequent periods), subject to
continued availability of funds and progress achieved.  Because the
nature and scope of the research proposed in response to this program
announcement may vary, it is anticipated that the size of an award will
vary also.

RESEARCH OBJECTIVES

Summary

Carefully controlled research studies are sought to investigate the
effectiveness and cost-effectiveness of drug abuse treatment linked to
criminal justice system involvement and delivered (1) prior to or in
lieu of prosecution or incarceration; (2) in the jail or prison setting
during the period of incarceration; (3) after release or during
transition from incarceration to release; or (4) for combinations of
these.  Research studies to investigate community-based
outreach/intervention behavioral change strategies in the population of
criminal-justice-involved drug users not in treatment will be
supported.  Of particular interest are research projects in geographic
areas having a high or unmet need for drug treatment services in the
criminal justice-involved population.

Background

The passage of new anti-drug abuse legislation and the strengthening of
existing laws have increased the already high risks of arrest and
incarceration for users of illicit drugs.  Data from the NIJ Drug Use
Forecasting (DUF) program show high rates of drug use among arrestees
sampled for drug testing.  Between April and June 1989, for example,
percentages in 13 metropolitan sites ranged from 56 percent positive in
Phoenix to 84 percent positive in Philadelphia.  According to the 1990
National Drug Control Strategy, an estimated 50 percent of Federal and
nearly 80 percent of State prison inmates have had experience with
drugs.  Likewise, it is estimated that 90 percent of institutionalized
juvenile offenders are drug abusers.

Although involvement with the criminal justice system may be considered
a powerful intervention in its own right, high rates of recidivism by
drug offenders suggest that incarceration alone is not sufficient to
prevent post-release return to drug use and drug-related crime.
Significant barriers to drug abuse treatment often exist in the
criminal justice system, including lack of resources, institutional
conflicts between security demands and treatment needs, recruitment and
retention of drug offenders in treatment, and problems implementing
effective treatment protocols.  Courts have few objective or systematic
means to identify those most likely to benefit from treatment or the
specific treatment most likely to be effective. Nevertheless, faced
with court mandates to reduce overcrowding, high rates of recidivism,
and State budgets that are shrinking while drug-related criminal costs
are escalating, many in criminal justice and elsewhere have recognized
the need to intervene effectively to treat drug abusers in the criminal
justice system.

There is an extensive history linking drug abuse treatment and the
criminal justice system.  Legislation passed in the 1960s by Federal
and State governments to provide for civil commitment of addicts to
treatment met with varying degrees of success (Leukefeld and Tims,
1988).  The California Civil Addict Program (CAP), which coupled drug
abuse treatment with a period of intensive supervision, was one of the
more successful of these programs (McGlothlin et al., 1977).  A variety
of other programs, including diversionary, pre-trial/pre-sentencing
programs such as Treatment Alternatives to Street Crime (TASC; Cook et
al., 1988), jail- or prison-based programs, and treatment as a
condition of parole, have been implemented, many without rigorous
evaluation.

In general, research on CJS-involved drug abuse treatment clients
suggests that treatment is effective in reducing drug use and criminal
activity while the client is in treatment and for some time thereafter.
The Stay-n-Out program, a comparison of prison-based milieu and
therapeutic community treatment, found that inmates in treatment
between 9 and 12 months had the best outcomes (Wexler et al., 1988).
The Treatment Outcome Prospective Study (TOPS; Hubbard et al.,
1989:132-133) found that clients with criminal justice involvement were
retained longer in community-based treatment than those with no legal
involvement and reported less drug use in the year after treatment.
There is some evidence from TOPS that early intervention, such as the
compulsory treatment of juvenile offenders and others not heavily
invested in the drug/crime culture, may be particularly beneficial in
interrupting evolving drug using and criminal careers.

Program Description

Applicants are advised to review existing information relevant to drug
abuse treatment of CJS-involved populations and to design controlled
clinical studies to determine the impact of providing drug abuse
treatment to CJS-involved clients.  Areas of research interest include
the following:

General

o  Improvement of treatment outcomes for individuals under legal
sanction.

o  Joint effects of criminal justice sanctions and treatment.

o  Strategies to increase retention, improve participation in
treatment, and reduce relapse to drug use and recidivism to criminal
activity.

o  Effectiveness of drug abuse treatment intervention strategies for
the drug-abusing juvenile offender.

Pre-Incarceration

o  Characterization and assessment of criminal justice clients most
likely to benefit from drug abuse treatment.

o  The effectiveness of matching criminal justice clients to
appropriate treatment.

o  Effectiveness of treatment in lieu of prosecution/incarceration in
reducing drug use, reducing criminal behavior, and increasing
productive activities.

o  Effect of legal pressure on client treatment compliance and outcome
variables.  For example, does drug testing increase compliance with
treatment or improve outcomes?

Institution-Based

o  Effectiveness and cost-effectiveness of institution-based treatment
approaches, including effectiveness of treatment beyond the period of
incarceration, and strategies to maintain and increase treatment gains
after return to the community.

o  Increasing the effectiveness of treatment delivered early in an
individual's period of incarceration.

o  Overcoming barriers to implementation of effective treatment within
the institutional setting, and effect of institutional incentives and
disincentives on treatment outcomes.

o  Relationship of inmate characteristics and criminal backgrounds to
treatment compliance and outcomes.

Post-Incarceration

o  Improvement of the effectiveness of drug abuse treatment and
aftercare in halfway houses and similar transitional programs charged
with re-integrating former inmates into the community.

o  Effectiveness of treatment after release compared with non-treatment
alternatives such as intensive supervision and monitoring, parole
supervision, and release without supervision.

o  Treatment program and client factors which predict relapse to
illicit drug use and recidivism to drug-related criminal activity.

Community-Based

o  Community-based outreach/intervention behavior change strategies,
especially in out-of-treatment individuals, to reduce illicit drug use
and drug-related risks such as HIV, TB, STDs, and re-involvement in the
criminal justice system/process.

o  Efficacy of community-based outreach/intervention strategies to
improve health and to reduce drug use and criminal behavior among youth
and adults at different stages of involvement in the criminal justice
system/process.

The importance of a sound research plan and qualified research staff
cannot be over-emphasized.  It is recommended that investigators use
the most rigorous methodology consistent with the purposes of the
research.  If controlled trials are not feasible, other types of
controls may be used, including case controls, equivalent comparison
groups, regression-discontinuity, or other designs.  Although many
treatment or criminal justice agencies have a research department,
those who do not may wish to enter into collaboration with
well-qualified researchers.  All applications are strongly urged to
address issues of project feasibility and collaborative arrangements,
study design, sampling procedures, implementation of the intervention,
instrumentation and measurement, data collection, quality control,
tracking of clients, followup, 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 being at risk for HIV acquisition or
transmission.  In high risk populations, investigators are encouraged
to assess the effects of new interventions on the acquisition and
transmission of infectious diseases, including HIV.

STUDY POPULATIONS

NIH POLICY CONCERNING INCLUSION OF MINORITIES AND WOMEN AS SUBJECTS IN
RESEARCH

Applications for clinical research grants and cooperative agreements
that involve human subjects are required to include minorities and both
genders in study populations so that research findings can be of
benefit to all persons at risk of the disease, disorder, or condition
under study; special emphasis should be placed on the need for
inclusion of minorities and women in studies of diseases, disorders,
and conditions which disproportionately affect them.  This policy
applies to all research involving human subjects and human materials,
and applies to males and females of all ages.  If one gender and/or
minorities are excluded or are inadequately represented in this
research, particularly in proposed population-based studies, a clear
compelling rationale for exclusion or inadequate representation should
be provided.  The composition of the proposed study population must be
described in terms of gender and racial/ethnic group, together with a
rationale for its choice.  In addition, gender and racial/ethnic issues
should be addressed in developing a research design and sample size
appropriate for the scientific objectives of the study.

Applicants are urged to assess carefully the feasibility of including
the broadest possible representation of minority groups.  However, NIH
recognizes that it may not be feasible or appropriate in all research
projects to include representation of the full array of United States
racial/ethnic minority populations (i.e., American Indians or Alaskan
Natives, Asians or Pacific Islanders, Blacks, Hispanics).
Investigators must provide the rationale for studies on single minority
population groups.

Applications for support of research involving human subjects must
employ a study design with minority and/or gender representation (by
age distribution, risk factors, incidence/prevalence, etc.) appropriate
to the scientific objectives of the research.  It is not an automatic
requirement for the study design to provide statistical power to answer
the questions posed for men and women and racial/ethnic groups
separately; however, whenever there are scientific reasons to
anticipate differences between men and women, and racial/ethnic groups,
with regard to the hypothesis under investigation, applicants should
include an evaluation of these gender and minority group differences in
the proposed study.  If adequate inclusion of one gender and/or
minorities is impossible or inappropriate with respect to the purpose
of the only study population available, there is a disproportionate
representation of one gender or minority/majority group, the rationale
for the study population must be well explained and justified.

The NIH funding components will not make awards of grants, cooperative
agreements or contracts that do not comply with this policy.  For
research awards which are covered by this policy, awardees will report
annually on enrollment of women and men, and on the race and ethnicity
of subjects.

Human Subjects Protections for Research Involving Prisoners

Activities carried out under this announcement may be governed by DHHS
Regulations for the Protection of Human Research Subjects (45 CFR 46).
These regulations require awardees to establish procedures for the
protection of human subjects involved in any research activities.
Projects involving prisoners require special additional protections in
accordance with Subpart C of the DHHS regulations.

Prior to funding and upon request of the Office for Protection from
Research Risks (OPRR), prospective awardees not holding an
OPRR-approved Multiple Project Assurance must file a Single Project
Assurance with OPRR and establish or identify an Institutional Review
Board (IRB) to review and approve the procedures for carrying out any
human subjects research occurring in conjunction with this award.  A
formal request for the required Assurance will be issued by OPRR at an
appropriate point in the review process, and examples of required
materials will be supplied at that time.  However, applicants may wish
to contact OPRR (301-496-7041) to obtain preliminary guidance on human
subjects issues.  When calling OPRR, applicants should identify
themselves as having questions about research involving prisoners.

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS 398
(rev. 9/91) and will be accepted at the standard application deadlines
as indicated in the application kit.  The receipt dates for
applications for AIDS-related research are found in the PHS 398
instructions.

Application kits are available at most institutional offices of
sponsored research and may be obtained from the Office of Grant
Inquiries, Division of Research Grants, National Institutes of Health,
Westwood Building, Room 240, 5333 Westbard Avenue, Bethesda, Maryland
20892, telephone 301/496-7979).  The title and number of the
announcement must be typed in Section 2a on the face page of the
application.

The completed original and five permanent, legible copies of the PHS
398 form must be submitted to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

REVIEW PROCEDURES

Applications received under this announcement will be assigned to an
initial review group (IRG) in accordance with established PHS referral
guidelines.  The IRGs, consisting primarily of non-Federal scientific
and technical experts, will review the applications for scientific and
technical merit in accordance with the standard NIH peer review
procedures.  Notification of the review recommendations will be sent to
the applicant after the initial review.  Applications will receive a
second-level review by an appropriate National Advisory Council, whose
review may be based on policy considerations as well as scientific
merit.  Only applications recommended for further consideration by the
Council may be considered for funding.

AWARD CRITERIA

Applications recommended for further consideration by an appropriate
Advisory Council will be considered for funding on the basis of overall
scientific, clinical, and technical merit of the proposal as determined
by peer review, appropriateness of budget estimates, program needs and
balance, policy considerations, adequacy of provisions for the
protection of human subjects, and availability of funds.

INQUIRIES

Written and telephone inquiries are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues related to treatment
research to:

Bennett W. Fletcher, Ph.D.
National Institute on Drug Abuse
5600 Fishers Lane, Room l0A-30
Rockville, MD  20857
Telephone:  (301) 443-4060

Direct inquiries regarding programmatic issues related to
community-based behavioral change research to:

Richard H. Needle, Ph.D., M.P.H.
National Institute on Drug Abuse
5600 Fishers Lane, Room 9A-30
Rockville, MD  20857
Telephone:  (301) 443-6720

Direct inquiries regarding fiscal matters to:

Ms. Shirley Ann Denney
Chief, Grants Management Branch
National Institute on Drug Abuse
5600 Fishers Lane, Room 8A-54
Rockville, MD  20857
Telephone:  (301) 443-6710

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, Sections 301 and 405, and administered under PHS policies
and Federal Regulations at Title 42 CFR 52, Grants for Research
Projects; Title 45 CFR Part 74 & 92, Administration of Grants; and 45
CFR Part 46, Protection of Human Subjects.  Title 42 CFR Part 2,
Confidentiality of Alcohol and Drug Abuse Patient Records, may also be
applicable to these awards.  This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review.

References

Cook, L.F., Weinman, B.A., et al.  Treatment Alternatives to Street
Crime.  In C.G. Leukefeld and F.M. Tims (eds.)  Compulsory treatment of
drug abuse: Research and clinical practice.  NIDA Research Monograph
86.  DHHS Pub. No. (ADM)88-1578.  Washington, DC:  U.S. Government
Printing Office, 1988.

Hubbard, R.L., Marsden, M.E., Rachal, J.V., Harwood, H.J., Cavanaugh,
E.R., and Ginzburg, H.M.  Drug abuse treatment:  A national study of
effectiveness.  Chapel Hill, NC:  University of North Carolina Press,
1989.

Leukefeld, C.G., and Tims, F.M. (Eds.).  Compulsory treatment of drug
abuse: Research and clinical practice.  NIDA Research Monograph 86.
DHHS Pub. No. (ADM)88-1578.  Washington, DC:  U.S. Government Printing
Office, 1988.

McGlothlin, W.H., Anglin, M.D., and Wilson, B.D.  Evaluation of the
California Civil Addict Program.  NIDA Services Research Monograph
Series, DHEW Pub. No. (ADM) 78-558.  Washington, DC: Superintendent of
Documents, U.S. Government Printing Office, 1977.

Wexler, H.K., Falkin, G.P., Lipton, D.S., Rosenblum, A.B., and Goodloe,
L.P. A model for prison-based drug treatment:  An evaluation of the
"Stay'n Out" therapeutic community.  (Final Report, NIDA Research Grant
R18 DA03310.)  NY:  Narcotic and Drug Research, Inc., 1988.