Full Text DA-98-003
 
STRATEGIC PROGRAM FOR INNOVATIVE RESEARCH ON COCAINE (AND OTHER
PSYCHOMOTOR STIMULANTS) ADDICTION PHARMACOTHERAPY (SPIRCAP)
 
NIH GUIDE, Volume 26, Number 21, June 20, 1997
 
RFA: DA-98-003
 
P.T. 34

Keywords: 
  Addiction 
  Drugs/Drug Abuse 
  Pharmacology 

 
National Institute on Drug Abuse
 
Letter of Intent Receipt Date:  October 14, 1997
Application Receipt Date:  November 14, 1997
 
PURPOSE
 
This Request for Applications (RFA) will support 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 cocaine and other
psychomotor stimulants use) and long-term (to prolong abstinence)
pharmacotherapies for the treatment of cocaine and other psychomotor
stimulants addiction.  A Strategic Program for Innovative Research on
Cocaine (and other psychomotor stimulants) Addiction Pharmacotherapy
(SPIRCAP) can focus its therapeutic research activities on, for
example, modulating specific receptor sites, (e.g., the dopamine
transporter, D3 receptor, a serotonin receptor, etc,) or
neurotransmitters that are believed to be involved in cocaine and
other psychomotor stimulants addiction, or on development of
biologically based anti-cocaine medications, such as antibodies,
enzymes, and catalytic antibodies, or on advancing the
neurobiological understanding of cocaine and other psychomotor
stimulants addiction that will construct new therapeutic concepts.
Studies submitted in response to this RFA should have a truly novel
or innovative approach.  The SPIRCAP Program thus complements
existing, more traditional preclinical and clinical programs for the
development of cocaine and other psychomotor stimulants treatment
medications, managed by the Medications Development Division of NIDA
[e.g., the Medications Development Research Units (MDRUs, P-50)], 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
of ground-breaking research from advanced preclinical findings to
clinical application in developing an anti-cocaine and other
psychomotor stimulants medication.  A SPIRCAP is encouraged to
include investigators from commercial (pharmaceutical, chemical, or
biotechnological companies) 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 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 (U19s).  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 SECTION VIII: 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, e.g., 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 companies)
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, the NIDA has not announced its intent to reissue the
RFA, awardee 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 $2.0 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 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 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 indirect costs).  Budget
requests should be carefully justified and commensurate with the
complexity of the project. Although this program is provided for in
the financial plans of the 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
 
The NIDA and the PHS are currently supporting comprehensive
extramural and intramural projects aimed at the elucidation of
processes susceptible to the action of cocaine and other psychomotor
stimulants and the mechanisms through which cocaine and other
psychomotor stimulants affects the fundamental brain processes, and
for developing safe and effective behavioral and pharmacological
therapies to treat cocaine and other psychomotor stimulants addicts.
Notwithstanding these efforts, no pharmacotherapeutic approaches yet
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.  The sense of urgency
is prompted by the fact that cocaine abuse and dependence affect all
segments of our society with devastating personal, social, and public
health consequences.  National surveys indicate that more than 23
million Americans have used cocaine at some time in their lives and
more than 1.3 million are current cocaine users.  Cocaine use is
associated with potentially life-threatening cardiovascular effects;
sex-for-crack exchanges that are spreading the AIDS virus among both
drug-abusing and non-drug-abusing populations; possible damage to the
health and development of infants born to women who abuse cocaine
during pregnancy; and violence and neighborhood disintegration
related to the cocaine marketplace.
 
In recent years, the scientific information base on the neurobiology
of cocaine and other psychomotor stimulants addiction has expanded
and the number of technological breakthroughs has increased
significantly. Advances in molecular biology, medicinal chemistry,
immunology and neuroscience of cocaine and other psychomotor
stimulants addiction have been made: genes for the dopamine and
serotonin receptors have been cloned, novel cocaine congeners of
varying affinities and pharmacokinetics properties have been
synthesized and evaluated, animal models which permit the study of
behavioral features of cocaine and other psychomotor stimulants
addiction in the laboratory are available, relationship among protein
function and regulation, brain structures, functions and behavioral
end points, and how cocaine and other psychomotor stimulants affects
these relationships have been elucidated, basic brain mechanisms
associated with addiction behavior have been studied by clinicians,
imaging scientists and psychologists.
 
However, application of 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 cocaine and other 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 and other psychomotor stimulants addiction.  The theme of
this program complements and balances present efforts pursued under
existing NIDA programs, including the Medication Development Research
Units (MDRUs), 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 the SPIRCAP Program
 
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 cocaine and other psychomotor stimulants addiction; and
(ii) implement pilot clinical studies of a therapeutic strategy.  In
line with this objective, the SPIRCAP Program 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 the SPIRCAP Program. 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:
 
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 (the
methadone, LAAM and naltrexone) or the nicotine addiction
pharmacotherapies (the nicotine patch, gum, etc.), however, the
differences between these addictions warrant further validations of
such concepts. Strategies that validate the utility of novel classes
of compounds as potential anti-cocaine and other psychomotor
stimulants medications, e.g., dopamine D1 antagonists, SSRIs, or
kappa opioid compounds.
 
Strategies that validate the utility of an anti-craving medication to
prevent relapse to cocaine and other psychomotor stimulants
addiction.
 
Strategies to validate the utility of novel medications to
ameliorate, reverse the development of  neuropsychiatric sequelae of
chronic cocaine and other psychomotor stimulants abuse as anti-
cocaine and other psychomotor stimulants addiction pharmacotherapy.
 
Strategies for the development of catalytic antibodies and anti-
idiotype based vaccines to treat cocaine addiction.
 
Strategies that validate the utility of compounds which interrupt
chronic cocaine and other psychomotor stimulants use based on
identified neurobiological and cellular mechanisms that may promote
repeated cocaine and other psychomotor stimulants use.
 
Strategies that validate the utility of compounds that modify cocaine
and other psychomotor stimulants sensitization or tolerance to treat
cocaine and other psychomotor stimulants addiction.
 
Strategies that explore the impact of other co-abused substances,
e.g. nicotine, alcohol on the neurobiology of cocaine and other
psychomotor stimulants addiction and the construct 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 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 VA interagency agreement.  It is envisioned that extended
clinical studies of treatments developed by a SPIRCAP group can be
accommodated under the clinical trial mechanisms available through
Medications Development Division.  However, these resources are
limited.  Queries about these programs should be directed to Dr.
Betty Tai at the address listed under INQUIRIES.
 
E.  The Group's objectives and goals should be relevant to and
compatible with the NIDA Program missions and directions as stated in
this RFA. Applicants should describe their plans to accommodate the
stated SPIRCAP Program requirements, criteria, and NIDA involvement.
 
F.  Applications that are not truly innovative or 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; (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), Medication
Development Research Units (MDRU), 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 is
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, and 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;
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 SPIRCAP, below.
 
INVENTION - An innovative therapeutic approach that is or may be
patentable under Title 35 of the United States Code.
 
(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 investigators from academic and/or non-profit research
institutions as well as scientists from commercial organizations,
performing research on interactive projects whose central focus is
development of effective pharmacotherapies for cocaine and other
psychomotor stimulants addiction. A CORE component cannot be used
toward fulfillment of the three research projects requirement.
 
NIDA SPIRCAP PROGRAM DIRECTOR - A Senior Scientist of the NIDA
extramural staff who coordinates NIDA's participation in the SPIRCAP
Program, oversees the operation of the entire SPIRCAP Program,
maintains the program stewardship duties and who ensures that the
SPIRCAP Program is consistent with the Medications Development
Program and NIDA missions and goals.
 
NIDA SCIENTIFIC COORDINATORS - Scientists of the extramural staff of
the Medications Development Program, NIDA, who function as
collaborators with the Principal Investigators and Project Leaders
and who facilitate the partnership relationship between NIDA and each
Group.  Two Scientific Coordinators from the Medications Development
Program - 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.
 
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 operates 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.
 
SPIRCAP GROUP STEERING COMMITTEES - Each SPIRCAP Group will form a
Steering Committee (SC) which is the primary coordination center of
the GROUP and will decide all major scientific/programmatic
decisions.  It will be composed of the Principal Investigator, the
Project leaders of the Group, the Chief of NIDA MDD Regulatory
Affairs Branch (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 FDA and/or DEA
officials) as needed.  Only one NIDA Scientific Coordinator will
vote. The SC will have the following responsibilities and
authorities: 1) 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) Identify/allocate the
essential and additional studies or resources (toxicology,
formulation) required for the IND targeted preclinical medication
development activities. 3) 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).
4) develop policies on data sharing, on access to data and materials
and on 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.)
 
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.
 
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 the 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, analyze and publish
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 under C. NIDA staff responsibilities.
 
Awardee will participate on the SPIRCAP Steering Committee as
described under 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 Chief of the NIDA Regulatory Affairs Branch (or designee) as the
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). 4) to develop policies on data sharing,
on access to data and materials and on publication authorship.  The
steering committee will meet two to four times a year and tele-
conference 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
Medications Development Program:  one coordinator will be from the
Cocaine Treatment Discovery Program, and one coordinator will be from
the Clinical Cocaine Treatment Program or other related Programs.
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 Chief of Regulatory Affairs Branch will serve as
the Program Director oversees the operation of the entire SPIRCAP
Program, maintains the program stewardship duties and who ensures
that the SPIRCAP Program is consistent with the Medications
Development Program and NIDA missions and goals.  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 three fold: 1) By means of their project management and
information management expertise to facilitate the effective
communication among study laboratories to ensure expedited transition
of ground-breaking research from advanced preclinical findings to
applied clinical mode.  2) To provide pharmaceutical regulatory
advice and support to the GROUP by serving as liaison with the Food
and Drug Administration (FDA) and Drug Enforcement Administration
(DEA) regarding all relevant regulatory issues; serving as
consultants for the GROUP to prepare IND submissions and to conduct
studies that meet FDA standards (GLP, GMP, GCP) when needed. 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 will not participate 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 existing regulations 37 CFR 401,
grantee/contractor organization must promptly report all inventions
disclosed to them by their investigators to 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
OMB 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 have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513), and in the
NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume 23,
Number 11.
 
LETTER OF INTENT
 
Prospective applicants are asked to submit, by October 14, 1997, 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 and to avoid conflict
of interest in the review process.
 
The letter of intent is to be sent to:
 
Director
Office of Extramural Program Review
National Institute on Drug Abuse
5600 Fishers Lane, Rm 10-42
Rockville, MD 20857
Telephone: (301) 443-2755
 
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 a
separate budget as a research project grant (R01). The research grant
application form PHS 398 (rev. 5/95) must be used in applying for
these cooperative agreements.  Applications kits are available at
most institutional offices of sponsored research and 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:
ASKNIH@odrockm1.od.nih.gov.  The title and number of this RFA must be
typed in Item 2 on the face page of the application.
 
o  An Introductory Section should be written for the proposed SPIRCAP
application describing it as a whole with respect to the overall
theme, goals, objectives, and overall research plan.  The
Introductory Section, not to exceed three pages, should contain
germane information on i) the overall research theme, leadership role
of the PI, 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) development timelines and milestones
for each projects in a graphic outline to clearly layout the sequence
of research events and how it related to each other, iii) the
proposed Principal Investigator or his/her institution as evidence of
capability to carry out the scientific and administrative duties
required in this RFA and the functions of the PI's central operations
office.
 
o  The proposal, depending on the nature of the program, should also
contain documents of i) justification of an IRB waiver if the
proposed clinical project will commence later after the completion of
the proposed preclinical studies, ii) assurance of the accessibility
and availability of the proposed test compounds, iii) plan for
clinical data management and adverse event reporting (AER).
 
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, TO ENSURE THE IDENTIFICATION OF YOUR
APPLICATION WITH THIS RFA the "Yes" box must be marked in item 2a of
the face page of the application form and the title and number of
this RFA typed.  Applications that are not received as a single
package from the Principal Investigator and which do not conform to
the instructions contained in PHS 398 (rev. 5/95) 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:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC-7762
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for courier/overnight 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
Telephone: (301) 443-2755
 
Applications must be received by November 14, 1997.  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.  Simultaneous
submission of identical applications will not be allowed, nor will
essentially identical applications be reviewed by different review
committees.  This restriction supersedes an NIH policy permitting
concurrent submission of a duplicate R01 and a component of a multi-
project application.  The NIH policy however, further stipulates that
should both the R01 and the multi-project application be considered
for funding, the R01 will be relinquished in favor of the multi-
project application.
 
REVIEW CONSIDERATIONS
 
A.  Review procedures
Applications will be reviewed by NIDA staff for completeness and
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 indirect) in
excess of $1.0 million will be returned without review unless the
applicant has received a written waiver from the NIDA to exceed this
amount (see FUNDS AVAILABLE, above).
 
Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate peer
review group convened 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 NIDA.
 
B.   Review Criteria:
 
The review group will review the program as an integrated research
effort focussed upon 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 review group will assess the scientific and technical merit of
the proposal according to the following criteria and assign one
overall priority score for the entire program.
 
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; Appropriateness and adequacy of the proposed
research approach, methodology, and plans to address the special goal
of the SPIRCAP.
 
The cohesiveness of a multi-disciplinary and multifaceted scope of
the program and coordination of individual projects and core(s);
 
The likelihood that innovative preclinical therapeutic strategies
will be refined and pilot clinical research implemented within two
years of award date;
 
The leadership, scientific ability, and administrative competence of
the Principal Investigator for the development, implementation, and
management of a comprehensive preclinical and clinical research
program; and the Principal Investigator's commitment to devote
substantial time and effort to the program;
 
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 and mechanisms for the
allocation of funds for day to day management, long term planning and
periodic evaluation, contractual agreements, and procedures for the
replacement of key personnel, e.g., the Principal investigators, if
required on an interim or permanent basis.
 
The qualifications, experience, and commitment of the investigators
responsible for the individual research projects or core(s) (Project
Leaders) and their contribution to the program, including their
ability to devote adequate time and effort to the 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) effort by the Principal Investigator and each Project Leader
should be devoted to the study, unless there are compelling arguments
to the contrary;
 
Availability of the resources necessary to perform the research;
 
Appropriateness of the proposed budget and duration in relation to
the proposed research;
 
Appropriateness of proposed methodology and demonstrated willingness
to work as part of the cooperative study and with NIDA Collaborating
Scientists;
 
Documented commitment of Institutions represented by Group members;
documented capability of Principal Investigator's Institution to
serve as the Central Operations Office for the Group;
 
Adequacy of provisions for the protection of animal and human
subjects; and
 
Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the specific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.
 
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;
 
Significance and originality of the proposed research;
 
Appropriateness of budget estimates;
 
Compatibility of research and data analytic approaches,
administrative structures, and other features to make a successful
cooperative study a reasonable likelihood;
 
Program priorities; and
 
Availability of funds.
 
SCHEDULE
 
Letter of Intent Receipt Date:     October 14, 1997
Application Receipt Date:          November 14, 1997 Scientific
Review Date:            January/February 1998 Council Meeting Date:
          May 1998
Earliest Award Date:               July 1998
 
INQUIRIES
 
Inquiries concerning this RFA are encouraged.  The opportunity to
clarify any issues or questions from potential applications is
welcome.
 
Direct inquiries regarding programmatic issues to:
 
Betty Tai, Ph.D.
Medications Development Division
National Institute on Drug Abuse
Parklawn Building, Room 11A-55
5600 Fishers Lane
Rockville, MD   20857
TEL:  (301) 443-3318/1428
FAX:  (301) 443-2599
Email: BTAI@NIH.GOV
 
Direct inquiries regarding fiscal matters to:
 
Gary Fleming, J.D., M.S.
Chief, Grants Management Branch
National Institute on Drug Abuse
Parklawn Building, Room 8A-54
5600 Fishers Lane
Rockville, Maryland  20857
TEL:  (301) 443-6710
Email:  gfleming@aoada1.ssw.dhhs.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 of 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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