STRATEGIC PROGRAM FOR INNOVATIVE RESEARCH ON COCAINE (AND OTHER PSYCHOMOTOR
STIMULANTS) ADDICTION PHARMACOTHERAPY (SPIRCAP)

Release Date:  May 13, 1999

RFA: DA-00-001

P.T.

National Institute on Drug Abuse

Letter of Intent Receipt Date:  July 26, 1999
Application Receipt Date:  August 25, 1999

PURPOSE

The Medication Development Division, National Institute on Drug Abuse, invites
applications to further the medication development efforts by supporting 
innovative, integrated preclinical and clinical research to validate novel
approaches and identify potential compounds that are safe and effective, short-
term (to reduce and stop stimulants use) and long-term (to prolong abstinence)
pharmacotherapies for the treatment of cocaine, methamphetamine, and nicotine
addiction. Studies submitted in response to this Request for Applications (RFA)
should have a truly novel and innovative approach.

A Strategic Program for Innovative Research on Cocaine (and Other Psychomotor
Stimulants) Addiction Pharmacotherapy (SPIRCAP) complements existing, more
traditional preclinical and clinical programs managed by the Medications
Development Division (MDD) of NIDA [e.g., the Medications Development Research
Units (MDRUs), the Medications Development Centers (P-50s), the medicinal
chemistry synthesis contracts, and the preclinical medications testing
contracts].

Of greatest significance, each SPIRCAP applicant is required to form a
collaborative enterprise between preclinical and clinical scientists in the
conceptualization and proof-of-concept of an identified therapeutic strategy. 
This will entail interactive research and information exchange between
preclinical and clinical investigators in order to ensure effective development
and refinement of the therapeutic concept.  The applicant's Group (defined in
Section VII) must, therefore, possess the expertise necessary to (i) evaluate the
proposed strategy in preclinical systems, and (ii) conduct pilot clinical
study(ies) using the proposed therapeutic approach.  A SPIRCAP should be
dedicated to the expedited transition from advanced preclinical research to
clinical testing of promising therapeutics to treat psychomotor stimulants
addiction.  A SPIRCAP is encouraged to include investigators from commercial
(pharmaceutical, chemical, or biotechnological) organizations.

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 RFA, Strategic Program for Innovative
Research on Cocaine (and Other Psychomotor Stimulants) Addiction Pharmacotherapy,
is related to the priority areas of "tobacco, alcohol and other drugs, and HIV
infection."  Potential applicants may obtain a copy of "Healthy People 2000"
(Full Report:  Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary
Report:  Stock No. 017-001-00473-1) through the Superintendent of Documents,
Government Printing Office, Washington, D.C.  20402-9325  (telephone
202-512-1800).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic (foreign applications are not accepted) 
for-profit and nonprofit organizations, private and public, such as universities,
colleges, hospitals, laboratories, units of state or local governments,
pharmaceutical companies, and eligible agencies of the federal government. 
Racial/ethnic minority individuals, women, and persons with disabilities are
encouraged to apply as Principal Investigators.

MECHANISM OF SUPPORT

Awards will be made as Cooperative Agreements (U19).  The Cooperative Agreement
is an assistance mechanism in which substantial NIDA programmatic involvement
with the recipient during the performance of the planned activity is anticipated. 
The nature of NIDA staff participation is described in SPECIAL REQUIREMENTS -
"TERMS AND CONDITIONS OF AWARD."  The awardee will be responsible for the
planning, direction, and execution of the proposed project and interrelated
activities.  All applications must consist of at least three interrelated
projects conducted by at least three independent research laboratories; for
example, a preclinical laboratory, a clinical laboratory, and a laboratory from
a pharmaceutical or biotechnology company.  For the purpose of this RFA, two (or
more) projects within a single company, or projects within the same academic
department, will not be considered independent. If there is an overlap of
(academic) departmental appointments of co-investigators, an explanation should
be provided about the independence of the projects.  The involvement of
laboratories from commercial (pharmaceutical, chemical, or biotechnological)
organizations as part of the project is encouraged. This limitation on the number
of independent projects from the same academic or private sector organization is
intended to increase the diversity and multi-disciplinary expertise available to
the Group from other than the parent institution or organization.  While no
maximum number of projects is stipulated, it has been observed that when a multi-
disciplinary grant or award exceeds six component projects, the program becomes
less coordinated and more difficult to manage.

This RFA is a one-time solicitation.  If by the end of the third year of the
award NIDA has not announced its intent to reissue the RFA, awardees should
contact NIDA program staff and consider submitting investigator-initiated (R01)
applications which will compete with all investigator-initiated applications and
be reviewed according to the customary peer review procedures.  All policies and
requirements that govern the grant program of the U.S. Public Health Service
(PHS) and the National Institutes of Health (NIH) apply.

FUNDS AVAILABLE

NIDA has set aside $3.0 million total costs for the first year of funding.  This
level of support is dependent on the receipt of a sufficient number and diversity
of applications of high scientific merit.  Two to three awards are anticipated
for project periods of up to four years.  However, support beyond the second year
of each SPIRCAP will be determined by NIDA staff based, in part, on the
recommendations of an external ad hoc committee convened to evaluate
accomplishments and to determine whether stated goals have been met.

Because the nature and scope of the research proposed in response to this RFA may
vary, it is anticipated that the size of individual awards will vary also. 
Awards are subject to a first year limit of $1.0 million in total costs (direct
plus F&A costs).  Budget requests should be carefully justified and be
commensurate with the complexity of the project.  Although this program is
provided for in the financial plans of NIDA, awards pursuant to this RFA are
contingent upon the availability of funds for this purpose.  Applications in
excess of $1.0 million total cost will be returned without review, unless a
waiver has been granted by the SPIRCAP Program Director, Dr. Betty Tai, in
advance of submission. (Address listed under INQUIRIES).

RESEARCH OBJECTIVES

Background

NIDA is currently supporting comprehensive extramural and intramural projects
aimed at the elucidation of processes susceptible to the action of psychomotor
stimulants (e.g., cocaine, methamphetamine, and nicotine) and the mechanisms
through which psychomotor stimulants affect the fundamental brain processes, and
is developing safe and effective behavioral and pharmacological therapies. 
Notwithstanding these efforts, no pharmacotherapeutic approaches have been proven
effective.  To address this critical deficiency, NIDA has made the development
of an anti-cocaine and other psychomotor stimulants medication its number one
priority.

In recent years, the scientific information base on the neurobiology of cocaine,
methamphetamine, and nicotine addiction has expanded, and the number of
technological breakthroughs has increased significantly. Advances in molecular
biology, medicinal chemistry, immunology, and neuroscience of cocaine,
methamphetamine, and nicotine addiction have been made.  These advances include
(1) genes for the dopamine and serotonin receptors have been cloned, (2) novel
cocaine congeners of varying affinities and pharmacokinetics properties have been
synthesized and evaluated, and (3) animal models which permit the study of
behavioral features of psychomotor stimulants addiction in the laboratory are
available.  Relationship among protein function and regulation, brain structures,
functions and behavioral end points, and how psychomotor stimulants affect these
relationships have been elucidated. Basic brain mechanisms associated with
addiction behavior have been studied by clinicians, imaging scientists, and
psychologists.

However, application of these developments to clinical and treatment activities
has not been commensurate with this expansion.  There is a need to apply these
research advances to clinical research studies, an effort that requires
interactive (interdependent) research activities involving both preclinical and
clinical investigators in the planning and implementation of studies whose
ultimate goal is an effective pharmacotherapy for psychomotor stimulants
addiction.  A concerted effort to mobilize the nation's combined basic and
clinical scientific expertise through SPIRCAP can accelerate advances in the
development of effective treatments for this brain disorder.

The SPIRCAP is specifically designed to support research for the development of
innovative hypothesis generating and proof-of-concept pharmacological
interventions and strategies for the treatment of cocaine, methamphetamine, and
nicotine addiction.  The theme of this program complements and balances present
efforts pursued under existing NIDA programs, including the Medication
Development Research Units (MDRUs), Medication Development Centers (P-50s), and
the various contracts managed by the Division's discovery programs for the
synthesis, testing, and screening of potential pharmacotherapeutics.

Research Goals and Objectives of SPIRCAP

A.  The principal goals of this RFA are to (i) bring together innovative,
advanced preclinical research of sound scientific rationale and clinical proof-
of-concept of an identified therapeutic strategy for psychomotor stimulants
addiction; and (ii) implement pilot clinical studies of a therapeutic strategy. 
In line with this objective, SPIRCAP will support projects with a common thematic
goal for which advanced preclinical data exist.  These efforts are to be
implemented through a concerted, interactive (interdependent) group effort by
components comprising the SPIRCAP Group.

B.  Applicants for SPIRCAP funding are expected to have an identified strategy -
- based on creative, solid, scientific rationale and supported by advanced
preclinical data - - which is proposed for pilot clinical evaluation. 
Therapeutic strategies that require studies in humans, as well as preclinical
studies to refine the clinical approach, are appropriate for funding under
SPIRCAP. Each SPIRCAP application must propose a well-defined, central research
focus consistent with the research objectives of the Program as stated in the
RFA.  The following approaches are provided as examples and are not intended to
be inclusive or restrictive:

o  Strategies that substantiate or refute the concept of "substitution-agonist"
and/or "antagonist" therapies.  Much of the current approaches for the
development of anti-cocaine medications are modeled after the success of opioid
addiction pharmacotherapies (methadone, LAAM and naltrexone) or the nicotine
addiction pharmacotherapies (nicotine patch, gum, etc.); however, the differences
between these addictions warrant further validations of such concepts.

o  Strategies that validate the utility of novel classes of compounds as
potential psychomotor stimulants medications; e.g., dopamine D1 antagonists,
SSRIs, or kappa opioid compounds.

o  Strategies that validate the utility of an anti-craving medication to prevent
relapse to psychomotor stimulants addiction.

o  Strategies to validate the utility of novel medications to ameliorate or
reverse the development of  neuropsychiatric sequelae of chronic psychomotor
stimulants abuse.

o  Strategies for the development of catalytic antibodies and anti-idiotype based
vaccines to treat psychomotor stimulants addiction.

o  Strategies that validate the utility of compounds which interrupt chronic
psychomotor stimulants use based on identified neurobiological and cellular
mechanisms that may promote repeated psychomotor stimulants use.

o  Strategies that validate the utility of compounds that modify psychomotor
stimulants sensitization or tolerance to treat psychomotor stimulants addiction.

o  Strategies that explore the impact of other co-abused substances (e.g.,
nicotine, alcohol) on the neurobiology of psychomotor stimulants addiction and
the construction of new therapeutic strategies to effectively accommodate these
factors.

C.  Applications should address advanced preclinical refinements of the proposed
strategy; evaluation and demonstration of therapeutic benefit in laboratory
animals, if applicable; and implementation of pilot clinical studies.  The cyclic
flow of information between preclinical and clinical phases is critical for
maximal refinement and optimization of the proposed clinical modality, clinical
evaluation of the therapeutic concept, and ultimately, to accelerate transition
to clinical treatment. (Applicants are encouraged to include women and children
whenever possible in early stage clinical concept testing.)

D.  Studies required for the IND-targeted preclinical development (formulation,
toxicology) of proposed treatments are generally beyond the scope of this RFA,
but such development through private venture capital is encouraged. 
Alternatively, a Group may request that the NIH assist in these developmental
tasks using some of the existing NIH/NIDA contract resources.  In addition,
NIDA/MDD also has the capacity for clinical evaluation of therapies for cocaine
addiction in its Interagency Agreement with the Veterans Administration.  It is
envisioned that extended clinical studies of treatments developed by a SPIRCAP
Group can be accommodated under the clinical trial mechanisms available through
MDD.  However, these resources are limited.  Queries about these
programs/resources are strongly encouraged and should be directed to Dr. Betty
Tai, MDD, NIDA, prior to the submission.  (Dr. Tai's address is listed under
INQUIRIES).

E.  The Group's objectives and goals should be relevant to and compatible with
NIDA's program missions and directions as stated in this RFA.  Applicants should
describe their plans to accommodate the stated SPIRCAP requirements, criteria,
and NIDA involvement.

F.  Applications that are covered by other NIDA programs are excluded from this
RFA and will be returned to the applicants.

G.  Relevance to other NIDA programs:  This RFA will support innovative,
integrated preclinical and clinical studies to validate therapeutic concepts for
cocaine and other psychomotor stimulants addiction.  Other MDD/NIDA initiatives
involving only preclinical studies for novel intervention strategies address (i)
preclinical animal models development; and (ii) early preclinical discovery of
new drugs and therapeutic approaches for the treatment of cocaine addiction. 
SPIRCAP applicants must ensure that no overlap exists between the specific aims
proposed under this RFA and those proposed under any of the other initiatives
referenced above, if applicable.

SPIRCAP applicants from an institution receiving government funds under General
Clinical Research Centers (GCRC) or Medication Development Research Units
(MDRUs), should describe how these programs are integrated with the proposed
studies and ensure that no scientific and budget overlap exists with the SPIRCAP
proposal.

DEFINITIONS

Administrative Core - An administrative facility that provides central
operations, support, and leadership for the overall management, integration,
communication, and coordination of the cooperative agreement and services shared
by the Group as a whole.  The Administrative Core should have a budget separate
from that of the Principal Investigator's research project, but should be
administered by the Principal Investigator's organization.  The Administrative
Core will have in its budget for each year travel expense to support its SPIRCAP
Steering Committee members to attend scheduled Steering Committee meetings.  The
Administrative Core will be responsible for allocating required travel expenses
to appropriate members of the Group.  Only SPIRCAP-related travel will be
supported under this RFA; travel funds to other domestic or foreign meetings are
not provided under this RFA.  (For additional details of required travel see 
SPECIAL REQUIREMENTS - TERMS AND CONDITIONS OF AWARD:  A. and B.)

Cooperative Agreement - An assistance mechanism in which substantial NIDA
programmatic involvement is anticipated with the recipient organization during
the performance of the planned activity.

Core Components - Resources for exercising leadership and coordination, as well
as laboratory facilities for equipment and services which are shared by two or
more projects of the SPIRCAP.  Examples of core components are:  biochemical,
cell-based, and immunological studies; animal model studies;
pharmacology/toxicology studies; and scale-up synthesis of the therapeutic agent. 
The core can be defined as a facility laboratory with established techniques and
assays which performs a service function resulting in an economy of effort and
savings in the overall costs of the Group.  The core unit is to be described with
the same detail as the research projects to enable evaluation of its scientific
merit.

Core Leader - The leader of one of the Scientific or Administrative Cores of the
SPIRCAP.

Group - see definition for SPIRCAP below.

Invention - An innovative therapeutic approach that is or may be patentable under
Title 35 of the United States Code.

NIDA Scientific Coordinators - Scientists of the extramural staff of the MDD,
NIDA, who function as collaborators with the Principal Investigators and Project
Leaders and who facilitate the partner relationship between NIDA and each Group. 
Two Scientific Coordinators from the MDD -- one from the preclinical program area
and one from the clinical program or other related program area -- will be
assigned to each Group by the SPIRCAP Program Director.  The Scientific
Coordinators are the immediate contact persons to the Group.

NIDA SPIRCAP Program Director - A Senior Scientist of the NIDA extramural staff
who coordinates NIDA's participation in the SPIRCAP, oversees the operation of
the entire SPIRCAP, maintains the program stewardship duties, and ensures that
the SPIRCAP Program is consistent with the program of MDD and the missions and
goals of NIDA.

Principal Investigator - The person who assembles the SPIRCAP, who is responsible
for the performance of the Group as a whole and for that of each of the Project
Leaders, and who is responsible for submitting the single application in response
to this RFA.  The Principal Investigator will coordinate Group activities
scientifically and administratively and should be the project leader of one of
the Research Projects of the Group and must commit at least 20 percent effort to
the Program.  The awardee (Principal Investigator's) institution establishes and
manages the central operations office that funds Group members and is legally and
fiscally accountable for the disposition of funds awarded.

Project Leader - The leader of one of the scientific research projects of the
SPIRCAP who is responsible for the scientific conduct of that project.

Research Project - A discrete, specified, circumscribed project that must relate
to the overall theme (refinement and proof-of-concept of high-risk innovative
pharmacological intervention and strategy for the treatment of cocaine and other
psychomotor stimulants addiction) of the SPIRCAP.

SPIRCAP Group Steering Committees - Each SPIRCAP Group will form a Steering
Committee (SC) which is the primary coordination center of the Group and will
make all major scientific/programmatic decisions.  The Committee will be composed
of the Principal Investigator, the Project Leaders of the Group, the NIDA SPIRCAP
Program Director (non-voting), the NIDA Scientific Coordinators (one from the
preclinical area and one from the clinical area), and other non-voting
consultants [e.g., scientists, relevant Food and Drug Administration (FDA) and/or
Drug Enforcement Administration (DEA) officials] as needed.  Only one NIDA
Scientific Coordinator will vote. The SC will have the following responsibilities
and authorities:  1) to develop a detailed plan and timetable to coordinate the
various research activities among the GROUP's various research laboratories to
ensure the preclinical concept/strategy will advance into clinical studies in a
timely fashion.; 2) to identify/allocate essential and additional studies or
resources (toxicology, formulation) required for the IND targeted preclinical
medication development activities; 3) to formulate strategies to successfully
interact with the FDA, and/or local IRBs, etc., regarding the IND submission and
quality control of the studies (GLP, GCP, GMP, etc); and  4) to develop policies
on data sharing, access to data and materials, and publication authorship. The
SC will meet at least two but not to exceed four times a year and will tele-
conference when requested. (For additional details on SC see SPECIAL REQUIREMENTS
- TERMS AND CONDITIONS OF AWARD: B.)

(SPIRCAP) Strategic Program for Innovative Research on Cocaine (and Other
Psychomotor Stimulants) Addiction Pharmacotherapy - In this RFA the terms
Strategic Program for Innovative Research on Cocaine (and Other Psychomotor
Stimulants) Addiction Pharmacotherapy (SPIRCAP) and "Group" are synonymous.  Each
Group may consist of a number of scientific investigator, from academic and/or
non-profit research institutions as well as scientists from commercial
organizations, performing research on interactive projects whose central focus
is the development of effective pharmacotherapies for psychomotor stimulants
addiction.  A CORE component cannot be used toward fulfillment of the three
research projects requirement.

SPECIAL REQUIREMENTS: TERMS AND CONDITIONS OF AWARD

NOTE:  Failure to abide by any of the Terms of Award pertaining to awardee
responsibilities stipulated in this section may result in withholding of funds
by NIDA until compliance with the Terms is restored.

A.  Awardee Rights and Responsibilities

Specifically, the Principal Investigator defines the details for the project
within the guidelines of the RFA; retains primary authority and responsibility
for the plan, conduct, analyses, and publication of results, interpretations and
conclusions of their studies; and agrees to accept assistance in coordination,
cooperation, and participation of NIDA staff in those areas of scientific and
technical management identified below under Section C, NIDA Staff
Responsibilities.

Awardee will participate on the SPIRCAP Steering Committee as described below
under Section B, Collaborative Responsibilities.  Awardee will retain custody of
primary rights to their data developed under the award, subject to rules
formulated by the Steering Committee, and government rights of access consistent
with current DHHS, PHS, and NIH policies.

B.  Collaborative Responsibilities

Under the Cooperative Agreement, a partner relationship exists between the
awardee and NIDA. In order to facilitate the collaborative effort between the
awardee and the NIDA extramural staff, a Steering Committee for each SPIRCAP will
be established.

Each SPIRCAP Steering Committee will be composed of:
1.  The Principal Investigator of the Group.
2.  The Project Leaders of all preclinical and clinical projects.
3.  The NIDA SPIRCAP Program Director.
4.  The NIDA preclinical and clinical Scientific Coordinators.
5.  Additional non-voting consultants as needed.

NIDA will have one vote and will not be serving as the Chair of the Committee.

Each SPIRCAP Steering Committee will have the following authority and
responsibilities:  1) to develop a detailed plan and timetable which will ensure
active and frequent interactions among the various research laboratories and NIDA
staff to expedite the  transition of preclinical concept/strategy into clinical
studies; 2) to identify and allocate all essential and additional studies or
resources (toxicology, formulation) required for the IND targeted preclinical
development; 3) to formulate strategies to interact with FDA, and/or local IRBs,
regarding the IND submission and quality control of the study (GLP, GMP, GCP,
etc.); and 4) to develop policies on data sharing, access to data and materials,
and publication authorship.  The Steering Committee will meet two to four times
a year and teleconference when requested by the awardee or by NIDA staff.

C.  NIDA Staff Responsibilities:  Nature of NIDA Participation

Assistance via a Cooperative Agreement differs from the traditional research
grant in that, in addition to the normal programmatic and administrative
stewardship responsibilities, the awarding component (NIDA) anticipates
substantial scientific and programmatic involvement during performance of the
research program.  NIDA shall work with each Group and shall be represented by
two NIDA Scientific Coordinators, both members of the professional staff of the
MDD; one coordinator will be from the MDD preclinical program area, and one
coordinator will be from the MDD clinical or other related program area.  NIDA
SPIRCAP Scientific Coordinators will be members of the SPIRCAP Steering Committee
and will not be serving as the Chair of the Committee. NIDA's SPIRCAP  Program
Director oversees the operation of the entire SPIRCAP, maintains the Program
stewardship duties, and ensures that the SPIRCAP Program is consistent with the
program of  MDD and the missions and goals of NIDA.  NIDA will have one vote.

In light of the complex structure and research activities of the SPIRCAP and the
medications development goal of the SPIRCAP, NIDA staff will provide technical
assistance and advice in the area of pharmaceutical regulatory science and in the
area of information management and project management to ensure effective and
efficient progress of the study.  Specifically, the responsibilities of NIDA
staff are threefold: 1) to facilitate the effective communication among study
laboratories to ensure expedited transition of groundbreaking research from
advanced preclinical findings to applied clinical mode by means of their project
management and information management expertise;  2) to provide pharmaceutical
regulatory advice and support to the Group by serving as liaison with the FDA and
DEA regarding all relevant regulatory issues; e.g., serving as consultants for
the Group to prepare IND submissions and to conduct studies that meet FDA
standards (GLP, GMP, GCP) when needed; and 3) to provide appropriate assistance,
advice, and guidance in general by participating in the design of Group
activities; advising in the selection of sources or resources; coordinating or
participating in collection and/or analysis of data and participating in the
preparation of publications; but not participating in the actual implementation
of the preclinical and clinical studies.

D.  Patent Coverage

Principal worldwide patent rights to an invention supported in whole or part with
federal funds usually vest with the grantee/contractor organization.  Under the
existing regulation 37 CFR Part 401, grantee/contractor organization must
promptly report all inventions disclosed to them by their investigators to the
NIH Extramural Technology Transfer Office.  A grantee can elect to retain title
to any subject invention, although such title is subject to an nonexclusive,
nontransferable, irrevocable, paid-up license to the Government to use, and
license others to use, the invention for government purposes.  If the grantee
does not elect to retain title, the government may do so.  Moreover, the
Government retains march-in rights that require the patent holders to license
others in certain circumstances, such as when the licensee has not taken
effective steps within a reasonable time to achieve practical application of an
invention or to alleviate a health and safety need.

E.  Arbitration Process

NIDA will establish an arbitration process to resolve any differences of opinion
between the awardee and NIDA on scientific and programmatic matters.  An
arbitration panel, composed of one Group designee, one NIDA designee, and a third
designee with expertise in the relevant area and chosen by the other two, will
be formed to review any scientific or programmatic issue that is significantly
restricting progress.  These special arbitration procedures in no way affect the
awardee's right to appeal an adverse action in accordance with PHS regulations
at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.

The special "TERMS AND CONDITIONS OF AWARD" described in this Section are in
addition to, and not in lieu of, otherwise applicable Office of  Management and
Budget administrative guidelines, HHS grant administration regulations at 45 CFR
Parts 74 and 92, and other HHS, PHS, and NIH grant administration policies.

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 is 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 on March 18, 1994,
Volume 23, Number 11.

Investigators may obtain copies of these documents from these sources or from the
program staff or contact person listed below.  Program staff may also provide
additional relevant information concerning the policy.

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 subject research conducted or supported by the NIH
unless there are scientific and ethical reasons not to include them.  This policy
applies to all NIH conducted or supported research involving human subjects. 
Details of the NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS
PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS can be found at
http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

LETTER OF INTENT

Prospective applicants are asked to submit by  July 26, 1999, a letter of intent
that includes a descriptive title of the overall proposed research; the name,
address, telephone number, and institution of the Principal Investigator; names
of prospective Project Leaders, other key investigators, and their respective
institutions; title, project leader, and institution for each component research
project; and the number and title of this RFA in response to which the
application is submitted.  Although the letter of intent is not required, is not
binding, and is not a factor in the peer review of the application, the
information it contains is helpful in planning for the review of applications. 
It allows NIDA staff to estimate the potential review workload.

The letter of intent should be sent to:

Director
Office of Extramural Program Review
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD 20892-9547
Rockville, MD  20852 (for courier/express services)
Telephone: (301) 443-2755
Fax:  (301) 443-0538

APPLICATION PROCEDURES

This RFA requires the submission of a single application for the proposed
SPIRCAP.  Because of the multi-institutional nature of a SPIRCAP and the special
requirements in this RFA, additional instructions regarding format are listed in
the following:

o  Each individual research project comprising the SPIRCAP Group application is
subject to the same format, 25 page limitation, and separate budget as a research
project grant (R01) application Form PHS 398 (rev. 4/98).  The research grant
application Form PHS 398 must be used in applying for these Cooperative
Agreements.  These forms are available at most institutional Offices of Sponsored
Research and also may be obtained from the Division of Extramural Outreach and
Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC
7910, Bethesda, MD 20892-7910; telephone 301-435-0714, Email: GrantsInfo@nih.gov. 
The title and number of this RFA must be typed in Item 2a on the face page of the
application.

o  The Research Plan should begin with an introduction for the proposed SPIRCAP
application describing it as a whole with respect to the overall theme, goals,
objectives, and research plan.  This Introductory Section, not to exceed three
pages, should contain germane information on i) the overall research theme,
leadership role of the PI, and mechanisms and plans to ensure effective
interactive research and information exchange between preclinical and clinical
investigators in order to ensure effective development and refinement of the
therapeutic concept; ii) the development timelines and milestones for each
projects in a graphic outline (Gantt and/or Pert charts) to clearly lay out the
sequence of research events and their relationship to each other, and the
critical go/no go criteria;  and iii) the proposed Principal Investigator or
his/her institution to evidence the capability to carry out the scientific and
administrative duties through a central operations office required in this RFA.

o  The proposal, depending on the nature of the program, should also contain a
special appendix with documents i) justifying an IRB waiver if the proposed
clinical project will commence after the completion of the proposed preclinical
studies; ii) assuring the accessibility and availability of the proposed test
compounds; iii) planning for clinical data management and adverse event reporting
(AER); and iv) proposing additional preclinical toxicology testing (performed by
NIDA/MDD resources) needed to file an IND to test the compound in man.

The RFA label available in the PHS 398 (rev. 4/98) 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 ENSURE THE
IDENTIFICATION OF YOUR APPLICATION WITH THIS RFA, the "Yes" box must be marked
in item 2 of the face page of the application form and the title and number of
this RFA be provided.  Applications that are not received as a single package
from the Principal Investigator and that do not conform to the instructions
contained in the PHS 398 (rev. 4/98) application kit will be judged
non-responsive and will be returned to the applicant.

The completed original, including the checklist, and three legible copies must
be sent or delivered 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)

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
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD  20892-9547
Rockville, MD 20852 (for courier/express services)
Telephone: (301)443-2755

Applications must be received by August 25, 1999.  If an application is received
after this date, it will be returned to the applicant without review.  If the
application submitted in response to this RFA is substantially similar to a grant
application already submitted to the NIH for review, the applicant will be asked
to withdraw either the pending application or the new one.

REVIEW CONSIDERATIONS

Review procedures

Applications will be reviewed by the Center for Scientific Review (CSR) for
completeness and by NIDA staff to determine programmatic responsiveness to this
RFA; those judged to be non-responsive will be returned to the applicant without
review.  Applications with first year total costs (direct and F&A) in excess of
$1.0 million will be returned without review unless the applicant has received
a written waiver from NIDA to exceed this amount (see FUNDS AVAILABLE, above).

Applications that are complete and responsive to this RFA will be evaluated for
scientific and technical merit by an appropriate peer review group convened by
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
priority score, and receive a second level review by the National Advisory
Council of Drug Abuse.

Review Criteria:

A scientific review panel will review the program as an integrated research
effort focussed on a central research strategy or theme, including the
relationship of research components to the central strategy/theme and the
effectiveness of the core units in supporting the program. The panel will
evaluate individual components and the overall program as an integrated effort
using the following criteria.

Program as an Integrated Effort

1.  The significance and originality of the overall proposed research program and
the development of a well defined central strategy relevant to the goals of the
RFA.

2.  The merit of the proposed overall research strategy, approach, methodology,
and plans to address the goal of the RFA. The likelihood that an innovative
preclinical therapeutic strategy for the development of medications to treat
stimulant addiction will be refined and pilot clinical research implemented
within two years of award date.

3.  The design of clinical plan to confirm hypothesis established by the pre-
clinical studies.

4.  The integration of multi-disciplinary and multifaceted components within the
thematic focus of the Program, and cohesion and coordination of individual
projects and core(s).

5.  The Principal Investigator's leadership, scientific ability, and
administrative competence, and commitment to devote substantial time and effort
for the development, implementation, and management of a comprehensive pre-
clinical and clinical research program. It is anticipated that, due to the
complexity and time required to maintain a well-coordinated and productive
research effort, a minimum 20% time and effort by the Principal Investigator
should be devoted to the study unless there are compelling arguments to the
contrary.

6.  The administrative arrangements and organizational structure, through an
Administrative Core, to facilitate and monitor the attainment of objectives and
internal quality control. For example, these factors will include plans to
enhance communication and cooperation among the investigators involved in the
program to establish mechanisms for the allocation of funds for day- to-day
management. A well designed management plan that clearly defines the lines of
authority, development timelines, and points of  'go' and 'no go' decisions, and
clearly demonstrates that resources will be used efficiently in reaching SPIRCAP
goals.

7.  The availability of the resources necessary to perform the research;
appropriateness of proposed methodology and demonstrated willingness to work as
part of the cooperative program and with NIDA Scientific Coordinators.

8.  The documented commitment of the institutions represented by Group members
and the documented capability of the Principal Investigator's institution to
serve as the Central Operations Office for the Group.

9.  The appropriateness and duration of the proposed budget in relation to the
proposed research.

Individual Projects

Individual project components will be evaluated further using the following
criteria:

1.  Significance:

The significance and originality of the proposed research and its relevance to
the central strategy of the application.  If the aims of the component are
achieved, how will the development of medication be facilitated?  What will be
the effects of these studies on the concepts or methods that drive the
development of medications?

2.  Approach:

The appropriateness and adequacy of the proposed research approach, methodology,
and plan to address the goal of the component.  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? Plans for the recruitment and
retention of subjects will also be evaluated, when relevant.

The assurance that hypothesis testing and experimental approach is supported by
a strong rationale and/or preliminary data.

The cohesiveness and coordination of individual projects and core(s) within the
multi-disciplinary and multifaceted scope of the program.

The reasonable assurance of accessibility of the test compounds proposed in the
study. A prerequisite for consideration of any study within an application is the
demonstrated access to the study compounds as well as necessary formulations as
required.  This includes necessary placebo forms of the test drug formulation.

3.  Innovation:

Does the project employ novel concepts, approaches or methods?  Are the aims of
the study original and innovative?  Does the project challenge existing paradigms
or develop new concepts?

4.  Investigators:

The scientific ability and expertise of the Project Leader. The qualifications,
experience, and commitment of the investigators responsible for the individual
research project(s) or core(s) (Project Leaders) and the contribution to the
program, including the ability to devote adequate time and effort to the
applicant Group.  It is anticipated that due to the complexity and time required
to maintain a well-coordinated and productive research effort, a minimum 20% time
and effort by each Project Leader should be devoted to the study, unless there
are compelling arguments to the contrary.

5.  Resources and Environment:

The availability of the resources and appropriate environment necessary to
perform the research and the willingness to work as part of the cooperative
program.

6.  Budget:

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

Core(s)

The evaluation of administrative and scientific cores will include the following
criteria:

1.  Significance:

The importance and value of the proposed cores?  What crucial support is provided
to the research projects?  Are the most efficient means identified?  How do they
enhance the effectiveness of individual projects?  Are mechanisms identified to
promote research collaborations, to develop new strategies, or to conduct pilot
experiments?

Are specialized substance abuse research clinics available?  Has the possibility
of an advisory steering committee been considered to evaluate progress of the
program?

What standardized tests, interventions, and evaluations are administered through
the core?  Are uniform operating systems proposed?  Does the plan give careful
consideration to overall timelines, choice and accessibility of medications,
patients recruitment issues, data management, and statistical resources? Is
interface with FDA and other regulatory agencies considered?

2.  Approach:

The effectiveness of administrative arrangements and organizational structure to
facilitate and monitor the attainment of objectives and internal quality control,
and plans to enhance communication and cooperation among the investigators
involved in the program.  Establishment of mechanisms for the allocation of funds
for day-to-day management.  A well-designed management plan that clearly defines
the lines of authority, development timelines, points of 'go' and 'no go'
decisions, and clearly demonstrates that resources will be used efficiently in
reaching SPIRCAP goals.

3.  Innovation:

Are innovative ways proposed in utilizing shared resources or benefiting from the
Principal Investigator's leadership to support research projects, retain
integrity, achieve efficiency, or minimize utilization of resources?

4.  Investigators:

The leadership and administrative capability of the Principal Investigator.

The need for an external advisory board.

5.  Environment:

The quality and adequacy of available resources necessary to perform the research
and the willingness to work as part of the cooperative program and with NIDA
Scientific Coordinators.

The documented commitment of the applicant institution and capability to serve
as the Central Operations Office for the program.

6.  Budget:

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

Other Considerations

1.  Adequacy of provisions for the protection human subjects and humane treatment
of animals  will also be considered.  The applications must conform to the
relevant NIH policies.  When an application involves potential adverse effects
on humans, the adequacy of the proposed means for protecting against such effects
must be demonstrated.

2.  The adequacy of plans to include both genders and minorities and their
subgroups, as appropriate, for the specific research goals and plan for the
inclusion of children will be part of scientific merit of the proposal.

AWARD CRITERIA

Applications recommended for further consideration by an appropriate Advisory
Council will be considered for funding based on the following factors:  overall
scientific and technical merit of the proposal as determined by peer review,
program priorities, and availability of funds.

SCHEDULE

Letter of Intent Receipt Date:  July 26, 1999
Application Receipt Date:       August 25, 1999
Scientific Review Date:         October/November 1999
Council Meeting Date:           January 2000
Earliest Award Date:            April 2000

INQUIRIES

Inquiries concerning this RFA are strongly encouraged.  Potential PIs are
encouraged to request contact the MDD Program Directors to discuss possible MDD
contract resources of preclinical toxicology testing and special regulatory
support.

Direct inquiries regarding programmatic issues to:

Betty Tai, Ph.D.
Medications Development Division
National Institute on Drug Abuse
6001 Executive Boulevard, Room 4123, MSC 9551
Bethesda, MD  20892-9551
Telephone:  (301) 443-1428/2397
FAX:  (301) 443-2599
Email: BTAI@NIH.GOV

Direct inquiries regarding fiscal matters to:

Gary Fleming, J.D., M.S.
Grants Management Branch
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3131, MSC 9541
Bethesda, MD  20892-9541
Telephone:  (301) 443-6710
Email:  gf6s@nih.gov

Direct inquiries regarding review matters to:

Teresa Levitin, Ph.D.
Office of Extramural Program Review
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD  20892-9547
Rockville, MD  20852 (for express mail)
Telephone:  (301) 443-2755
Email:  tl25u@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the catalog of Federal Domestic Assistance No.
93.279.  Awards are made under the authority 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 grant policies and Federal Regulations 42 CFR
Part 52 and 45 CFR Parts 74 and 92.  This program is not subject to the
intergovernmental review requirements of Executive Order 122372 or Health Systems
Agency Review.

The Public Health Service 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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