kristoff@GENBANK.BIO.NET (Dave Kristofferson) (09/06/90)
FEASIBILITY STUDIES FOR LARGE-SCALE DNA SEQUENCING OF
REGIONS OF HIGH BIOLOGICAL INTEREST
RFA AVAILABLE: HG-90-03
P.T. 34; K.W. 0755045, 1004000, 0755018
National Center For Human Genome Research
Letter of Intent Receipt Date: October 15, 1990
Application Receipt Date: December 3, 1990
The National Center for Human Genome Research (NCHGR)
invites applications for assistance awards to support
feasibility studies using advanced state-of-the-art DNA
sequencing technology to accomplish large-scale sequencing
projects at a higher rate and lower cost than is currently
possible.
This program is described in the Catalog of Federal Domestic
Assistance No. 13.172. Awards will be made under the
authority of the Public Health Service Act, Sections 301
(Public Law 78-410, as amended 42 U.S.C. 241) and
administered under PHS grants policies and Federal
Regulations 42 CFR Part 52 and 45 CFR Part 74. This program
is not subject to the intergovernmental review requirement
of Executive Order 12373 or to Health System Agency review.
BACKGROUND
The NCHGR sponsors basic and applied research concerned with
the development and application of new technologies for the
characterization and analysis of the human genome and the
genomes of important model organisms. The activities
encompassed by the NCHGR program include genetic and
physical mapping, DNA sequencing, and informatics related to
mapping and sequencing. The NCHGR, in conjunction with the
Department of Energy, recently formulated a five-year plan
that identifies areas where further research, including new
technology development, is needed before the
characterization of the human and other genomes can proceed
to the degree envisioned by the scientific community.
With respect to sequencing megabase regions of DNA, it is
clear that rates of sequence acquisition achievable today
must be increased at least 10- to 100-fold, and DNA
sequencing costs must be reduced at least 10-fold before
large-scale sequencing, on the order of a human chromosome,
can be considered. Current technology for DNA sequencing
includes both manual and automated methods. Sequencing DNA
by these methods is estimated to cost between $2 and $5
(total cost) per base pair. However, currently available
sequencing techniques and strategies have not been tested on
a large scale. Thus, it is possible that current or
improved methods, when used at the megabase level, and when
combined with economies of scale, new strategies, improved
automation, and/or new technologies, will significantly
lower the cost of DNA sequencing. The purpose of this
Request for Applications (RFA)
is to support investigator-initiated research projects that
will extend the limits of advanced state-of-the-art
technology considerably further than has yet been attempted.
DEFINITION OF LARGE-SCALE SEQUENCING
The Program Advisory Committee on the Human Genome has
suggested that, at the present time, a reasonable definition
of a "large-scale sequencing project" is one that attempts
to determine on the order of three megabase pairs of
(largely) contiguous sequence in three years (by comparison,
the largest DNA sequence completed to date is a viral genome
of 240 kilobase pairs, work that took several years to
complete). Continuity is an important characteristic of the
DNA sequence to be obtained; the scientific problems that
arise in considering sequencing a one-megabase region are
different from those involved in sequencing 1000 one-
kilobase regions. The Committee estimated that a rate of 2-
5 megabase pairs of DNA sequence per year in the subsequent
years should be attainable. Similarly, reduction of the
cost of DNA sequencing to approximately $0.75 per base pair
within three years and to $0.50 per base pair within five
years was recommended to be a reasonable guide. As these
levels are well beyond anything that has been achieved to
date, applicants are encouraged to consider them as
guidelines. The NCHGR encourages discussion of these
guidelines by applicants, including an estimate of whether
they can be achieved.
DATA MANAGEMENT
Another essential component of DNA sequencing projects that
also needs to be investigated on a large scale is data
management. Although software and database packages are
currently available for acquisition and assembly of DNA
sequence, they have been developed for relatively small-
scale applications. Thus, it is not known whether any of
these will be adequate for use in megabase sequencing
projects. It is understood that different sequencing
strategies will have different data handling needs and,
therefore, no one solution to data management problems for
large-scale sequencing is likely.
While, in the long run, software may have to be developed
for interpretation of the large segments of DNA sequence
generated by the human genome project, the informatics
priorities for this RFA will be primarily directed toward
the design, development, and testing of software for data
acquisition, assembly, and management.
RESEARCH SCOPE
Projects responsive to this RFA should test hypotheses and
new research strategies designed to yield information on the
feasibility of determining large amounts of DNA sequence
rapidly and in a cost-effective manner. It is anticipated
that such projects will involve an integrated approach that
addresses a number of identifiable aspects of the problem,
including:
o The biological materials to be sequenced, e.g.,
genomic DNA or overlapping clones representing a
megabase-sized region. Applicants are encouraged
to select DNA comprising regions of high
biological interest;
o Scale-up of DNA sequencing technology to allow
large-scale, high-throughput, and low-cost
acquisition of DNA sequence data. Note: in order
to have a uniform approach for estimating the cost
of sequencing, applicants should calculate the
cost per base of finished DNA sequence ready for
publication and/or submission to a public
database. The cost figure should include all
direct and indirect expenses, starting either
directly with the DNA of the organism or with
appropriately large fragments (YAC or cosmid
clones) and ending with the final finished
sequence. Neither the costs of any necessary
laboratory renovation nor the costs associated
with the interpretation of DNA sequence data
should be considered as a part of the per base
cost of sequence determination;
o Types of errors and rates of error that will occur
in large-scale DNA sequencing, and a discussion of
what level of error will be acceptable;
o Overall strategies, including quality control
systems, and plans for organizing the research
group;
o Systems for data acquisition, data management,
sequence assembly, and error estimation.
DATA RELEASE
The policy of the U.S. Public Health Service (PHS) states
that "when resources are developed with PHS funds and the
associated research findings have been published . . . it is
essential that they be made readily available for research
purposes to the scientific community." Applicants will be
expected to follow this policy. Generating large amounts of
DNA sequence will raise additional questions with respect to
data release and public accessibility to DNA sequence data
because much of this data will never be published in
journals or will not be published in its entirety. The
NCHGR considers the timely release of data to the scientific
community to be critical and encourages applicants to
release all sequence data, including those that are not
published, to a public database in a timely fashion. This
is an area of active discussion within the scientific
community. Although it will not be used as a review
criteria, the NCHGR is interested in the
investigator's analysis and evaluation of issues related to
the timely release of data, such as a timetable for data
release, the criteria for "finished" DNA sequence (i.e.,
sequence that is ready to be publicly released), and the
intervals (e.g., number of nucleotides or number of months)
at which data will be released.
MECHANISM OF SUPPORT
Support for this program will be through research grants
(R01s). Applicants may request up to five years of support.
For grants awarded for more than three years, competitive
renewals will be due at the end of the third year to allow a
determination of whether the project is satisfactorily
meeting its stated objectives. As a result of that review,
funds may be continued at the level recommended or reduced
to phase out the project by the end of the original project
period.
An annual meeting is being planned to assist grantees receiving
funds under this RFA in maintaining communication with other
investigators working on the development of large-scale DNA
sequencing methods and in obtaining rapid access to those
developments. Funds for
travel to this
meeting for as many as two investigators can be requested.
The total amount of support available for grants under this RFA
(approximately $6 million) is
contingent upon the appropriation of funds for this purpose.
It is anticipated that up to three awards will be made
during fiscal year 1991. There is no set limit on the size
of each award. Rather, each investigator should propose a
budget adequate to accomplish the work proposed. The number
of awards is contingent
upon the quality of the applications received; if there are
a large number of meritorious applications, consideration
will be given to increasing the number of awards. It is
possible that additional RFAs soliciting applications on
this topic may be published in the future.
LETTER OF INTENT
It is strongly recommended that potential applicants contact
NCHGR staff to discuss research objectives. Potential
applicants are asked to submit a letter of intent by October
15, 1990. This letter should include a descriptive title of
the proposed research, names of principal investigators and
other key investigators and their institutions. The
letter of intent is requested in order to provide an
indication of the number and scope of applications to be
reviewed. The letter of intent does not commit the sender
to submit an application, nor is it a requirement for
submission of an application. Letters of intent should be
sent directly to:
Dr. Jane L. Peterson
Chief, Research Centers Branch
National Center for Human Genome Research
Building 38A, Room 610
National Institutes of Health
Bethesda, MD 20892
Telephone: (301) 496-7531
E-mail: jp2@nihcu.bitnet; jp2@cu.nih.gov
APPLICATION AND REVIEW PROCEDURES
Applications in response to this announcement will be
reviewed in accordance with the usual NIH peer review
procedures. If the application submitted in response to
this RFA is substantially similar to a research grant
application already submitted to the NIH for review, but has
not yet been reviewed, 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. Therefore, an
application cannot be submitted in response to this RFA
which is essentially identical to one that has already been
reviewed. This does not preclude the submission of
substantial revisions of applications already reviewed, but
such applications must include an Introduction addressing
the previous critique.
Applications will first be screened for responsiveness to
this RFA by NIH staff. Those deemed nonresponsive will be
returned to the applicant. If a large number of responsive
applications is received, they will undergo a preliminary
peer review to identify the most meritorious ones.
Applications that are deemed non-competitive by this peer
review will receive only a brief critique and will not be
reviewed further. The remaining applications will be
reviewed for scientific and technical merit by an initial
review group (IRG) assembled by the Office of Scientific
Review, NCHGR. A second level of review will be conducted
by a national advisory council. Review criteria include the
following:
o Overall scientific and technical merit of the
research;
o The potential for the proposed work for
attaining the research objectives outlined in
this RFA;
o Training, experience, research competence,
and dedication of the investigator(s);
o Adequacy of available facilities;
o Provision for the protection of human
subjects and the humane care of animals; and
o Appropriateness of the requested budget for
the work proposed.
Applications should be submitted using the form PHS 398
(rev. 10/88). The RFA label available in the revised
application kit MUST be affixed to the bottom of the face
page. 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. Application kits are available in
the business or grants office at most academic or research
institutions, or from the Division of Research Grants,
National Institutes of Health. Applications will be
accepted in accordance with the following schedule:
TIMETABLE:
Receipt Date: December 3, 1990
IRG Review: Feb/March, 1991
Council Review: May 1991
Earliest Funding Date: July 1991
It is essential that applicants type "Feasibility Studies
for Large Scale DNA Sequencing of Regions of High Biological
Interest" and the RFA number HG-90-03 on line 2 on the face
page of the application form. The original and four copies
of the application should be submitted to the following
office:
Grant Application Receipt Office
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892**
To expedite the review process, it is important to submit
two copies of your application directly to:
Office of Scientific Review
National Center for Human Genome Research
Building 38A, Room 604
National Institutes of Health
Bethesda, MD 20892
Funding decisions will be based on recommendations of the
initial review group and the advisory council regarding the
scientific merit and program relevance. For more
information and the complete RFA, please contact:
Dr. Jane L. Peterson
Chief, Research Centers Branch
National Center for Human Genome Research
Building 38A, Room 610
National Institutes of Health
Bethesda, MD 20892
Telephone: (301) 496-7531
E-mail: jp2@nihcu.bitnet; jp2@cu.nih.gov
REQUEST FOR COOPERATIVE AGREEMENT APPLICATIONS:
RFA: AI-90-10
RE-ISSUANCE OF RFA 89-AI-18 DATED JUNE 30, 1989
NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR THE TREATMENT
OF OPPORTUNISTIC INFECTIONS ASSOCIATED WITH ACQUIRED IMMUNE
DEFICIENCY SYNDROME
P.T. 34; K.W. 0715008, 0740018, 0740020, 0755025, 1002008
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Letter of Intent Date: October 1, 1990
Application Receipt Date: December 10, 1990
The National Institute of Allergy and Infectious Diseases
(NIAID) invites applications for the establishment of
National Cooperative Drug Discovery Groups for the Treatment
of Opportunistic Infections Associated with Acquired Immune
Deficiency Syndrome (NCDDG-OI).
There are no present plans to reissue this Request for
Application (RFA) at any future time. The NIAID intends to invite
competitive renewal applications upon expiration of the
initial funding period, contingent on the continued
availability of funds for this purpose.
LETTER OF INTENT
Prospective applicants are asked to submit by October 1,
1990, a letter of intent that includes a descriptive title
of the overall proposed research, the name and institution
of the Principal Investigator, a title for each component
research project and brief descriptions of the proposed
projects. Names of prospective project leaders and other
key investigators and their respective responsibilities
should be included (maximum of two pages). The letter of
intent is requested in order to provide an indication of the
number and scope of applications to be reviewed and in order
to allow early preparations for review as well as promote
early interactions between applicants and NIAID staff. The
letter of intent does not commit the sender to submit an
application, nor is it a requirement for submission of an
application. The letter of intent should be sent to:
Dr. Margaret I. Johnston
Developmental Therapeutics Branch
Division of AIDS
National Institute of Allergy
and Infectious Diseases
6003 Executive Boulevard
Bethesda, MD 20892
Telephone Number: (301) 496-8197
I. BACKGROUND AND SUMMARY
The Acquired Immune Deficiency Syndrome (AIDS) is a
disease that destroys the body's capacity to defend itself
against a variety of infections. By April 1990, over
132,000 cases of AIDS had been reported in the United
States and more than 80,000 of these patients (61%) had
died. Recent projections indicate that between 850,000 to
1,000,000 persons in the United States may already be
infected with HIV, the infectious virus associated with
AIDS. Opportunistic infections (OIs) are the pathologic
consequence of AIDS; they are the most frequent causes of
morbidity and mortality in AIDS patients. OIs are the
principal cause of hospitalization of HIV-infected
individuals. The estimated total medical costs of AIDS
patients in the U.S.A. alone will be $21 billion by 1991.
Individuals infected with HIV are susceptible to a range of
protozoal, fungal, viral, and bacterial infections. While
Pneumocystis carinii, Candida albicans, Toxoplasma gondii,
herpesvirus (CMV, HSV), and Mycobacterium avium are the most
frequently reported opportunistic pathogens, recent reports
indicate that Cryptococcus neoformans and Cryptosporidium
are also prevalent in AIDS patients. The actual incidence
of OIs in HIV-infected individuals may
be higher than the reports would indicate as there are
inherent problems in diagnosing and recording these
infections. The following is a brief description of major
pathogens, currently available therapies, and deficiencies in
the clinical management of OIs in AIDS patients.
Pneumocystis carinii pneumonia (PCP) is the most serious
infection in AIDS patients; between 60-80% of AIDS
patients will develop this complication. In the past,
approximately 90% of untreated individuals died from this
infection. Recent studies, based on the phylogenetic
analysis of Pneumocystis 16S-like-RNA, indicate it to be a
member of the family of fungi.
Trimethoprim/sulfamethoxazole (TMP/SMX) and parenteral
pentamidine isethionate are the drugs that are used as
initial therapy. Particularly in AIDS patients, TMP/SMX
treatment is associated with the development of
hypersensitivity reactions and a high frequency of adverse
reactions. The Food and Drug Administration (FDA) has
approved aerosolized pentamidine for prophylaxis of PCP.
In the United States, 15 - 68% of the adult population are
seropositive for Toxoplasma gondii antibodies. In
immunocompromised individuals, reactivation of the
pathogen leads to encephalitis, which is fatal if
untreated. AIDS patients who are known to have antibodies
to T. gondii are at significant risk for developing
toxoplasmic encephalitis. At least 30% of AIDS patients
who are seropositive for T. gondii will ultimately develop
the disease. Current treatment is the combination of
pyrimethamine and sulfadiazine. However, the treatment is
limited by toxicity and lack of efficacy against the
latent cystic form of the parasite. Thus, the relapse
rate is high if therapy is discontinued. Recent studies
suggest that clindamycin, in combination with
pyrimethamine, may be effective against cerebral
toxoplasmosis in AIDS patients.
Cryptosporidium can cause enterocolitis and diarrhea,
malnutrition, and death in humans. Some of the known
antiprotozoal and antifungal agents, such as
TMP/SMX, pentamidine, ketoconazole,
and metronidazole, are ineffective against
cryptosporidiosis.
Fungal infections account for more than 50% of the
opportunistic pathogens seen in AIDS patients. Candida
albicans is the most common pathogen (80% of fungal
isolates). Candida species often cause oral and
pharyngeal thrush (mucosal candidiasis). Esophagal
candidiasis is also common, but disseminated infection is
rare. Cryptococcosis develops in 6 - 13% of patients with
AIDS. Recently, there has been an increase in the
reported cases of disseminated histoplasmosis caused by
Histoplasma capsulatum in patients with AIDS with a
history of residence or travel in endemic areas.
Current management of fungal infections in AIDS patients
has many problems. The diagnosis is often imprecise. The
most common therapy is amphotericin B (AMB); sometimes,
parenteral AMB is administered in combination with
5-flucytosine. Oral azoles, such as ketoconazole and
fluconazole, are currently under study in AIDS patients.
AMB is toxic and continued therapy is often required.
Some of the recent fungal isolates are not susceptible to
AMB. AMB is only partly effective against
coccidioidomycosis. Therefore, there is a need for more
selective antifungal agents.
Mycobacterium avium complex (MAC) is the most common cause
of bacterial infection in AIDS patients. It is an
intracellular pathogen and is characteristically
resistant to many antituberculosis agents except
ethambutol. Therefore, it is essential to identify
antimycobacterial agents that can penetrate cells,
particularly macrophages. Other agents that are effective
in vitro against MAC include ansamycin, clofazimine,
cycloserine, amikacin, ethionamide, imipenem and
ciprofloxacin. Unfortunately, these agents are not
bactericidal at concentrations achievable in plasma.
Recent studies suggest that combinations of
antimycobacterial agents with immunomodulators, such as
tumor necrosis factor (TNF), may be useful for treatment
of MAC infections.
Infection with human cytomegalovirus (HCMV), a member of the
herpesvirus group, represents a significant problem in AIDS
patients; it is considered to be the second most common
opportunistic infection in AIDS patients. The most common
clinical manifestation in AIDS patients is retinitis.
Greater than 90% of individuals with AIDS are seropositive
for HCMV. Recent reports indicate that HCMV might
contribute to the progression of AIDS. Certain regulatory
genes of HCMV are capable of increasing HIV gene expression
by transactivation. Ganciclovir (DHPG) has been shown to be
effective against HCMV infection. The drug, however, has
some toxic side effects and requires continuous treatment.
Furthermore, HCMV strains resistant to DHPG have been
isolated from patients receiving the therapy for a prolonged
period of time. There is clearly a need for more potent and
selective inhibitors to treat HCMV-induced diseases.
In summary, most opportunistic infections in AIDS patients,
especially Pneumocystis pneumonia and cryptococcal
meningitis, are life threatening if diagnosis and treatment
are delayed. Others, such as CMV, HSV, and Candida may
cause severe morbidity. The management of OIs in AIDS
patients is often difficult and complicated for various
reasons: (i) OIs are often present simultaneously with
other OIs; (ii) the pathogens may develop resistance to
conventional therapies; and (iii) the patients are more
susceptible to drug-related toxic reactions. It is
important to recognize that most of the currently available
therapies against OIs in AIDS patients either lack efficacy
or have potentially serious side effects. The severity and
long-term consequences of the opportunistic infections
underscore the need for more selective and potent
therapeutic agents against them. In addition, there is a
crucial need for studies on prophylaxis and maintenance
therapy for control of persistent and latent infections.
Six NCDDGs received awards in 1990. Pathogenic organisms
under study include P. carnii, T. gondii, Cryptosporidium,
M. avium, C. albicans, and C. neoformans. Research being
pursued by these Groups include identification of unique
molecular targets in opportunistic pathogens that are
exploitable in discovering selective therapeutic agents;
rational design of novel drugs; X-ray crystallography and
protein structure; biochemistry and metabolism of drugs;
animal model evaluation of potential therapies; molecular
biology of opportunistic pathogens; and immunotherapies.
II. OBJECTIVES AND SCOPE
The major goal of this RFA is to stimulate research
efforts leading to targeted discovery of agents effective
in the treatment as well as prophylaxis of OIs in AIDS
patients. No clinical trials will be supported. Research
efforts may be directed, but are not restricted, towards
controlling infections caused by the following pathogens:
Toxoplasma gondii, Cryptosporidium spp., Pneumocystis
carinii, pathogenic fungi (except Candida spp.),
Mycobacterium avium, and HCMV.
Research considered responsive to this RFA may include,
but is not necessarily restricted to, the following:
o studies to identify and characterize molecular
targets in opportunistic pathogens that may be
exploited in discovering selective therapeutic
agents;
o studies on the biochemical differences between the
selected pathogen and host cells. For example,
isolation and characterization of certain key enzymes
and identification of compounds that selectively
inhibit the enzymes from the pathogen;
o molecular genetic studies to identify differences
between the pathogens and mammalian cells; studies to
exploit the differences to identify selective
therapeutic agents;
o targeted synthesis of compounds that will selectively
interact with specific molecular targets;
o establishment and utilization of in vitro assay
systems (biochemical, biological) to identify active
agents (synthetic chemicals and biologicals including
natural products) that inhibit selected molecular
functions;
o studies on natural and treatment-induced emergence of drug-
resistant pathogens as it relates to targeted drug
approach.
The above-mentioned areas of investigations are
representatives of future possibilities. Investigators are
encouraged to explore other avenues to identify potential
therapeutic agents.
It is expected that no more than one Group each will be
funded for P. carinii and cytomegalovirus. Projects or
cores with proposed animal model development or efficacy
testing in animal models must be integrated within the major
goal of targeted drug discovery and required to attain the
Group's objectives. Funds for evaluation of new agents in
animal models will be withheld until compounds generated by
the Group are available for animal efficacy studies and be
limited to 25% effort of the Group. NOTE: Animal
component(s) may be requested by the NIAID to evaluate in
animal models compounds other than their own. When this
occurs, and in the event that this has not already been
done, the necessary funds for evaluation will be released.
If proposed, studies on combination therapies should be
limited to 25% of total effort of the Group. Projects
utilizing non-random screening of natural products,
biologics and/or synthetic compounds must not exceed 25% of
the total effort of the Group. Large-scale random screening
of compounds will not be supported under this RFA.
Studies required for the clinical development of
identified potential treatments are beyond the scope of
this RFA, but development through the private sector is
encouraged. Alternatively, an NCDDG may request that the
NIAID assist in these developmental tasks. The National
Institutes of Health (NIH) has a
contract program for the preclinical development of
compounds for the treatment of AIDS. The NIAID has
contracts for the evaluation of relevant therapies in
several animal models. In addition, the NIAID has awarded
47 AIDS CLINICAL TREATMENT UNITS (ACTUs) for Phase I,
Phase II, and Phase III clinical trials at 112 sites. It
is envisioned that these ACTU cooperative agreements will
be available for clinical studies of treatments discovered
under this initiative, upon the recommendation of the
NCDDG and concurrence of the AIDS Clinical Drug
Development Committee and the Division of AIDS.
III. MECHANISM OF SUPPORT
A. Awards will be made as COOPERATIVE AGREEMENTS.
NIAID, in awarding the Cooperative Agreement,
anticipates substantial programmatic staff
involvement during performance of the award. The
nature of NIAID staff assistance to the awardees is
described in Section VIII of this RFA under "TERMS OF
AWARD: NATURE OF PARTICIPATION OF NIAID STAFF".
There is no intent, real or implied, for NIH staff to
direct Group activities or to limit the freedom of
investigators. The interaction of academic and non-
profit research institutions with commercial
(including industrial) organizations and Government
is encouraged to favor the efficient invention of new
entities and strategies for AIDS treatment and to
facilitate their subsequent development to clinical
trial.
B. NIAID has set aside $2.0 - 2.5 million for the
initial year's funding of this RFA. The amount spent
will be dependent on the continuing availability of
funds for this purpose and the quality and diversity
of approved applications. Funding of 3-4 awards is
anticipated. The dollar value of NCDDG awards is
subject to the same limitation governing Program
Project grants. Current limit for a Program Project
is one million dollars in total costs, unless prior
approval by NIAID is obtained. The starting date for
the initial annual period will be on or after June 1,
1991.
[When the applicant institution is outside the United
States, awards will be limited to three years. When
the applicant institution is within the United States
and the application contains research projects in a
foreign country, the request for funding may be up to
five years.]
C. Awards will be made to successfully competing Groups
rather than to the individual scientists or
institutions comprising the Group. Support of all
Group activities will be coordinated through a
Central Operations
Office located within the applicant organization.
Each award will be made only to the Principal
Investigator's institution.
D. Under the Cooperative Agreement, a partner
relationship between the recipient of the award and
NIAID exists in which the Group is responsive to the
requirements and conditions set forth in this RFA.
Specifically, the Principal Investigator defines the
details for the project within the guidelines of the
RFA, retains primary responsibility for the
performance of the scientific activity, and agrees to
accept close assistance in coordination, cooperation,
and participation of NIAID staff in all aspects of
scientific and technical management of the project in
accordance with the terms formally and mutually
agreed upon prior to the award. It is presently
envisioned that the NIAID will be actively engaged in
the coordination of all components including
assisting the awardees in:
* cooperative participation in data analysis
and reporting;
* prior approval of changes of key personnel
including the Principal Investigator or
Project Leaders;
* retention of the option to withhold support
if a Project Leader withdraws from the
Group and a suitable replacement of key
personnel is not obtained.
E. All policies and requirements that govern the grant
program of the U.S. Public Health Service and the
NIH apply.
F. Although this program is provided for in the
financial plans of NIAID, the award of Cooperative
Agreements pursuant to this RFA is also contingent
upon the continuing availability of funds for this
purpose.
IV. DEFINITIONS
ARBITRATION PANEL - A group composed of the Principal
Investigator or Project Leader of a particular NCDDG as
the "Group" designee, one NIAID designee, and a third
designee with expertise in the relevant area and chosen by
the other two. The interaction of this panel is detailed
in Section VIII, "TERMS OF AWARD".
COOPERATIVE AGREEMENT - An assistance mechanism in which
substantial NIAID programmatic involvement with the
recipient organization during the performance of the
planned activity is anticipated.
CORE COMPONENT - Laboratory facilities for equipment and
services that shall be shared by two or more projects of
the NCDDG. Examples of core components are: biochemical
studies, screening studies, scale-up synthesis of drugs
(ten grams or less). The core can be defined as any
project with established techniques and assays which
perform a service function or results in an economy of
effort and savings in the overall costs of the NCDDG.
DISCOVERY - The term "discovery" is used explicitly to
limit activities of the NCDDG to preclinical
identification, design, and development of new entities.
INVENTION - A new drug or innovative treatment that is or
may be patentable under Title 35 of the United States
Code.
NATIONAL COOPERATIVE DRUG DISCOVERY GROUP (NCDDG) - In
this RFA the terms NATIONAL COOPERATIVE DRUG DISCOVERY
GROUP, NCDDG, and "Group" are synonymous. A number of
laboratory research projects representing diverse
scientific disciplines and organizations that join
together under a single Principal Investigator and that
function as a unit with a common goal: the
conceptualization, invention, and evaluation of new
entities and strategies for the treatment of OIs. Groups
must consist of at least two independent Projects
conducted by at least two independent laboratories. A
CORE COMPONENT cannot be used toward fulfillment of the
two Projects requirement.
NEW DRUG - In the context of the NCDDG-OI program, the
term "drug" is used broadly to encompass new synthetic
agents, natural and biological products as novel
therapeutic strategies or inventions designed to
effectively treat OIs in AIDS patients.
NIAID NCDDG PROGRAM DIRECTOR - A member of the NIAID
extramural staff who coordinates NIAID's participation in
the NCDDG Program. This responsibility includes: (i)
overseeing the entire NCDDG-OI program; (ii) assuring that
Groups' objectives are consistent with Program's and NIAID
mission and goals; (iii) assigning Scientific Coordinators
to appropriate Groups based on scientific expertise and
compatibility with the Group research interests; (iv)
assuring overall scientific balance among Groups in the
NCDDG Program; (v) networking and facilitating
collaboration between Groups and industry to expedite
development of promising anti-OI agents; (vi) keeping the
NCDDG Program current with regard to scientific
developments and breakthroughs; and (vii) identifying gaps
not adequately pursued.
NIAID SCIENTIFIC COORDINATOR - A member of the extramural
staff of the NIAID who functions as a peer with the
Principal Investigator and Project Leaders and facilitates
the partnership relationship between NIAID and the Group.
The Scientific Coordinator, based on his/hers scientific
expertise, interests, and compatibility with the Group's
areas of research, is assigned to the Group by the NCDDG
Program Director.
PRINCIPAL INVESTIGATOR - The person who assembles the
NCDDG, assembles a single application with the information
provided by the Project Leaders, submits the
application in response to this RF,A and is responsible
for the performance of the Group as a whole and each of
the Project Leaders. The Principal Investigator is very
strongly encouraged to lead one of the research projects
of the Group and is expected to coordinate Group
activities scientifically and administratively. The
Principal Investigator's (awardee) 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 NCDDG.
SCIENTIFIC ADVISORS PANEL - A panel, comprised of the
Scientific Coordinator and 2-3 peers from the scientific
community, whose mission is to provide the Principal
Investigator with a comprehensive review of the Group's
activities and progress, consult on future goals and
strategies, and recommend alternative directions, as
appropriate. Selection and appointment of the Panel is
the responsibility of the Principal Investigator. Members
of the Panel will not be affiliated with any of the
institutions comprising the Group. A Scientific Advisors
Panel is required only of Groups funded for more than
three years. The composition of the designated Panel will
be provided to the NIAID in the Noncompetitive Renewal
Application at the completion of year two of funding. The
Panel will provide the Principal Investigator a
comprehensive review of the Group's activity in years three
and four of funding. These reviews will encompass
timeliness of progress in individual projects relative to
original projections; progress relative to Group's
objectives and needs; continued relevance of a given
project to Group's goals; continued coordination of
Group's objectives with the objectives of the NCDDG
Program; and recommendations for new directions, as
appropriate.
V. COMPOSITION OF AN NCDDG-OI
A. The NCDDG-OI will consist of the following:
1. A Principal Investigator;
2. Project Leaders, each to head a research
project. The research projects will utilize
diverse scientific disciplines or alternative
disciplines that are appropriate to the
realization of Group objectives (e.g.,
microbiology, biochemistry, humoral immunology,
cellular immunology, structural biology,
biophysics, biochemistry, medicinal chemistry,
organic chemistry, etc.). Interdisciplinary
projects are encouraged;
3. A Scientific Coordinator designated from the
NIAID extramural staff;
4. (OPTIONAL) Core components that would provide
for laboratory facilities, equipment, and
services to be shared by two or more projects.
It may also include support for the costs of
administration, purchasing, and secretarial
services. Items described above that are
included in the institution's indirect cost
rate are subject to negotiations, based on
their applicability as direct or indirect
charges;
5. A Scientific Advisors Panel to be designated at
the end of year two of funding by Groups funded
for more than three years (see Section IV,
"DEFINITIONS: SCIENTIFIC ADVISORS PANEL"). The
Panel will work together with the Group,
evaluate and advise on Group's progress, future
goals, strategies, and new directions, as
appropriate. With the exception of the
Scientific Coordinator, members in the Panel
will not be affiliated with any of the
institutions comprising the Group.
B. The Principal Investigator, in addition to providing
scientific and administrative leadership, may have a
research project. Project Leaders will be directly
responsible to the Principal Investigator. The
formation of the Group, the application in response
to this RFA, the overall management of the Group, and
the allocation of funds to the various laboratory
projects will be the responsibility of the Principal
Investigator and the Principal Investigator's
institution in accordance with PHS policies.
C. The composition of the Group and its research
projects should depend on the talents required to
accomplish its scientific and technical objectives as
perceived by the Principal Investigator and Project
Leaders. The major consideration in structuring an
NCDDG should be the mobilization of maximum
intellectual strength and the ability to carry out
the proposed research.
D. An individual scientist may be proposed as a Project
Leader by more than one applicant as part of a CORE
COMPONENT. Project Leaders who do not have a core
function will not be supported by more than one
Cooperative Agreement awarded under this RFA unless
the research is clearly delineated in separate NCDDG
applications. Individuals currently supported under
an existing NCDDG-OI or other NCDDG programs may be
funded under this RFA as long as there is no
scientific or budgetary overlap in funded activities.
E. An NCDDG may have more than one project from one
institution. However, the varied talents and
commitment required for effective drug discovery are
not usually all present in one institution, and it is
anticipated that the Project Leaders within a Group
will be from several institutions.
F. A minimum of two but no maximum number of research
projects per Group is stipulated. However, the
Principal Investigator could experience difficulty in
providing the desirable level of guidance and Project
Leaders might communicate and collaborate less
efficiently if the Group were to contain more than
five or six research projects, including the
Principal Investigator's project.
G. In forming Groups, Principal Investigators should
remain cognizant of the need for communication,
including regular meetings of the members. While it
is not a requirement of this RFA, the formation of
Groups on a geographically regional basis may be
advantageous. This is a particularly important
factor to be considered by applicants from outside
the United States or if the applicant proposes
laboratory projects in foreign countries.
H. An NCDDG is encouraged to include scientists from
academia, non-profit institutions, and/or commercial
organizations. The active participation of industry
is encouraged because it will allow this sector of
the scientific community to contribute its
intellectual and material resources and will favor
expeditious development of effective anti-OI
therapies.
VI. RESEARCH GOALS AND SCOPE
A. The goals of the NCDDG-OI
are:
1. The conceptualization, discovery and
preclinical development of drugs and strategies
designed to effectively treat OIs in
individuals infected with the human
immunodeficiency virus;
2. The conduct of biological, biochemical, and
pharmacological studies leading to selection of
potential therapies; and
3. The recommendation of therapies, entities, or
strategies for development in clinical trials.
B. Applications for an NCDDG-OI should stress creative
approaches to the discovery of effective therapies to
treat OIs and should emphasize
the following:
1. specific objectives of the proposed NCDDG-OI;
2. research approaches to the realization of
objectives and the provision of comprehensive
information (including citations) in support of
the rationale(s) for the proposed approaches;
and
3. the scientific and technical areas of expertise
(Project Leaders) required to attain Group
objectives and the leadership ability of the
Principal Investigator.
C. The Group's objectives and goals should be relevant
and compatible with NIAID Program's missions and
directions as stated in this RFA.
VII. PATENT COVERAGE
Since the discovery of agents active against OIs in AIDS
patients is the objective of this effort, and since active
involvement by industrial laboratories is facilitated by
the existence of adequate patent coverage, it is essential
that applicants provide plans to assure such coverage.
With multiple institutions involved, the patent situation
could be complicated. Each applicant Group must,
therefore, provide a detailed description of the approach
to be used for obtaining patent coverage and for licensing
where appropriate, in particular where the invention may
involve investigators from more than one institution. In
addition each Group must provide a detailed description of
the procedures to be followed for the resolution of legal
problems that may develop. All Group members can be full
partners in the research and in any inventions resulting
therefrom. The specific patenting arrangements among the
institutions may vary, and could include joint patent
ownership and exclusive licensing arrangements.
Applicants are encouraged to develop an arrangement that
is most suitable for their own particular circumstances.
The proposed patent plan among the institutions comprising
the group MUST be included along with the application.
The patent agreement, signed and dated by the
organizational officials authorized to enter into patent
arrangements for each Group member and member institution,
must be sent before the application deadline to Dr.
Margaret I. Johnston, Chief, Developmental Therapeutics
Branch, Division of AIDS, 6003 Executive Boulevard,
National Institutes of Health, Bethesda, MD 20892.
Federal regulation clause 37CFR401 and HHS Inventions
regulations at 45 CFR Parts 6 and 8 require that NIH be
informed of inventions and licensing occurring under NIH-
funded research. Invention and licensing reports must be
submitted to Extramural Invention Reports Office, Office
of Extramural Research, Building 31, Room 5B41, NIH, with
a copy to Dr. Margaret I. Johnston, Chief, Developmental
Therapeutics Branch, Division of AIDS.
VIII. TERMS OF AWARD: AWARDEE RIGHTS AND RESPONSIBILITIES
AND NATURE OF NIAID 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 component awarding the Cooperative
Agreement anticipates substantial programmatic involvement
during performance of the project. However, the applying
Group must define its objectives and approaches in accord
with its own interests and perceptions of novel and
exploitable approaches to the discovery of effective
agents active against OIs in AIDS patients and must
develop the details of the research design following the
guidance given in this RFA. It is the primary
responsibility of the Principal Investigator to clearly
state the objectives and approaches of the Group, to plan
and conduct the research stipulated in the proposal, and to
ensure that the results obtained are analyzed and
published in a timely manner. The data obtained will be
the property of the awardee.
NIAID shall participate as a member of the Group and shall
be represented by a Scientific Coordinator. The
Coordinator shall be selected from the Developmental
Therapeutics Branch of the Division of AIDS and appropriate Branches
of the Division of Microbiology and Infectious Diseases of
the NIAID.
During performance of the award the NIAID Scientific
Coordinator may provide appropriate assistance by
participating in the design of group activities; advising
in the selection of sources or resources, replacement of
staff, etc.; coordinating or participating in collection
and/or analysis of data; advising in management and
technical performance; or participating in the preparation
of publications. However, the role of NIAID will be to
facilitate and not to direct the activities. It is
anticipated that decisions in all activities outlined
below will be reached by consensus of the Group and that
the NIAID Scientific Coordinator will be given the
opportunity to offer input to this process. The manner of
reaching this consensus and the final decision-making
authority will rest with the Principal Investigator.
Failure to abide by these Terms of Award may result in
withholding of funds by the NIAID.
A. Awardee Rights and Responsibilities
1. The Principal Investigator, Project Leaders,
and the NIAID Scientific Coordinator will meet
periodically to review progress, plan and
design research activities, and establish
priorities. The frequency of meetings (not
less than two per year) shall be determined by
the Principal Investigator who will be
responsible for scheduling the time and place
(generally at one of the performance sites),
notifying the Scientific Coordinator at least
forty-five days prior to the meeting date, and
preparing concise proceedings or minutes which
will be delivered to the members of the Group
including the Scientific Coordinator within
thirty days of the meeting. The NIAID
Scientific Coordinator will participate but not
chair Group meetings.
2. In addition to these two meetings, one meeting
each year will be held at the NIH Bethesda (or
at a site designated by NIAID) during which all
Principal Investigators and Project Leaders
will present significant findings in symposium
format.
The NCDDG annual meeting is one of the central
points for information flow among the Principal
Investigators, NCDDG Program Director, the
private sector, other drug development
concerns, and NIAID. The Program Director
consults with the Groups' key personnel in
formulating the overall agenda, selecting
session Chairs, and in identifying key topics
for discussion. Session Chairs select the
workshop participants who constitute the bulk
of invited speakers. This forum is central for
cross-fertilization of ideas, integration of
unique anti-HIV strategies, and a critical
source for updating Program and keeping it
abreast of scientific and technological
innovation toward the discovery of new anti-
viral modalities. Data presented at this
meeting are selected by the individual
presenters in consultation with their Principal
Investigator thus affording appropriate
protection of proprietary or commercially
sensitive information.
It is expected that selected NIH staff, members
of established committees and advisory boards,
and others active in the process of discovery
and development of therapies for opportunistic
infections will be invited to this meeting.
The Principal Investigator will have control
over the data and results presented by the
Group. Funds for attendance of these three
required meetings should be included in the
budget for each research project. The
application should also include plans for
scheduling Group meetings, notifying Group
members including the NIAID Scientific
Coordinator, and documenting and disseminating
Group meeting proceedings.
3. Groups funded for more than three years will
designate a Scientific Advisors Panel by the
end of year two of funding. The Principal
Investigator will convene a meeting or meetings
with the Panel in years two and three of funding.
The Panel will work together with the Group
and advise the Principal Investigator on the
Group's progress, future goals, strategies and
new directions, as appropriate. Members of the
Panel will not be affiliated with any of the
institutions comprising the Group. Funds to
cover expenses incurred by the Panel should be
included in the Administrative Core component
of the application.
4. A critical determinant of Group success will be
the degree of communication among its members.
Therefore, additional informal meetings among
all participants, as well as regular telephone
and written communication, will be important.
B. NIAID Assistance in Implementation and Management of
Research Activities
1. The NIAID Scientific Coordinator, like other
Group members, may suggest studies within the
scope of the Group's objectives and research
activities; may present to the Group
experimental findings from published sources or
from contract projects in support of these
suggestions; may participate in the design and
execution of experiments as agreed to by the
Group; and may participate in the analysis and
publication of results.
2. The NIAID Scientific Coordinator may assist the
Group or other individual members in research
planning, particularly with respect to:
a. reduction of duplication of efforts
conducted in other extramural projects;
b. provision of needed resources and
information that may not be otherwise
available to the Group; and
c. provision of data from testing conducted in
resource contract laboratories.
3. The Scientific Coordinator may serve as a
resource for information, laboratory testing,
and biological supplies (e.g., animals), when
such resources are not a normal requirement of
the Group's day-to-day research activities but
may be required on an occasional basis. The
following is a list of some resources that
may be available from the NIAID: these
resources are intended for initial studies and
will not be available on a continual basis.
(i) Reference compounds for standardization of
test systems, as analytical standards, and for
related purposes.
(ii) Materials for biological testing.
(iii) Laboratory testing capacity, whenever
appropriate and possible, in a current
contract-based preclinical therapy-
related laboratory testing program or
other NCDDGs. The Groups are expected to
provide sufficient test material for such
testing.
(iv) Searches of computer files of chemical
structures and biological activity, if
requests for such searches are sufficiently
focused to avoid excessive costs. Information
given to an NCDDG will be restricted by the
standard confidentiality agreements between
the Government and suppliers of test materials
to the Government.
(v) Experimental animals, when the occasional need
arises in Groups whose main research
activities do not require these materials on a
regular basis. Groups whose experimental
approach involves studies that require animals
on a regular basis must budget for costs to be
paid from award funding.
(vi) Computer processing and statistical
evaluations, if costs are not excessive.
(vii) Networking with other NIH staff, NCDDGs,
other collaborators, and other government
and non-government employees who may
provide guidance, expertise, or resources
to facilitate development of therapies
identified by the Group.
It is understood that the Government provides
its consulting and testing services in the
interest of promoting experimental anti-
infective agents through preclinical and
clinical testing and development in the most
expeditious fashion, and that newly marketed
agents that have utilized this service will be
offered to the public at a reasonable cost.
4. The NIAID Scientific Coordinator may assist
the Groups by providing them with compounds
for initial testing and for confirmatory
testing. In testing compounds supplied by the
NIAID, the Groups agree to abide by any
confidentiality agreement between the NIAID
and a third party who has supplied the
compounds for testing through NIAID.
C. Collection and Analysis of Data, Procedures for
Submission of Results to NIAID, and Preparation of
Group Findings for Presentation and Publication
In addition to the special reports and stipulations
described below, reporting requirements will be
identical to those currently in existence for awardees
of traditional NIH research project grants.
1. The principal end product of NCDDG-OI
activities will be the discovery of new
entities and strategies for development to
clinical trials for AIDS-associated OIs.
Subsequent developmental work through private
resources is encouraged. Alternatively, the
Group may recommend that development be
sponsored by NIAID. In the latter case, it
will be necessary for the Principal
Investigator, appropriate Project Leaders, and
NIAID to collaborate in the analysis,
summarization, preparation, and presentation
of data to the appropriate NIAID staff.
2. NIAID will retain the option to cross-file or
independently file an application for
investigational clinical trial; e.g., an
Investigational New Drug application (INDA) to
the United States Food and Drug Administration
of any invention resulting from these NIAID-
supported Cooperative Agreements. Reports of
data generated by the Group or any of its
members required for inclusion in INDAs and
Clinical Brochures and for cross-filing
purposes will be submitted by the Principal
Investigator to the Scientific Coordinator
upon request. Such reports will be in final
draft form and include background information,
methods, results, and conclusions. They will
be subject to approval and revision by NIAID
and may be augmented with test results from
other Government-sponsored projects prior to
submission to the appropriate regulatory
agency.
3. The Government, via the Program Director or
designated Scientific Coordinator, will have
access to data generated under this
Cooperative Agreement and may periodically
review the data and progress reports.
Information obtained from the data may be used
by the Scientific Coordinator for the
preparation of internal reports on the Group's
activities. However, the applicant will
retain rights to the data, and timely
publication of major findings is encouraged.
Publication or oral presentation of work done
under this agreement is the responsibility of
the Principal Investigator and appropriate
Project Leaders and will require appropriate
acknowledgement of NIAID support.
D. Inasmuch as certain activities under "TERMS of AWARD:
NATURE OF PARTICIPATION OF NIAID STAFF" require
approval by NIAID staff during performance of this
Cooperative Agreement (specifically, reports intended
for inclusion in INDAs and Clinical Brochures, change
in Principal Investigator or Program Leader,
redistribution of biological materials received
through the Scientific Coordinator and dissemination
of research findings resulting from the use of these
materials), NIAID will establish an arbitration
process to resolve any differences of opinion with
regard to programmatic matter. An arbitration panel,
composed of one Group designee, one NIAID 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. This arbitration
process in no way affects the right of an award
recipient to appeal selected post award administrative
decisions in accordance with HHS, PHS, and NIH
regulations and policies. 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.
E. The special "TERMS OF AWARD: NATURE OF PARTICIPATION
OF NIAID STAFF" 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 Part 74, and
other HHS, PHS, and NIH grant administration policy
statements.
IX. MINIMUM REQUIREMENTS FOR APPLICATION
Applicants seeking funding as an NCDDG-OI
must meet the following
requirements:
The application must be from a Group and must:
A. Name a single Principal Investigator who is an
employee of the applicant institution and who
will be responsible for the application, for
Group research activities, and for the support
of Group activities through a Central
Operations Office;
B. Identify the single applicant organization
(awardee institution) that will provide the
Central Operations Office and be legally and
financially responsible and be accountable for
the use and disposition of funds awarded on
the basis of this RFA; show availability of
personnel and facilities capable of performing
and supporting the administrative functions of
the NCDDG-OI;
C. Identify the Group as having an approach that
should be reviewed as being comprehensive,
immunological, biological, or synthetic in its
approach for the design of new treatments for
OIs in AIDS patients;
D. Provide a description of the Group's plan for
assuring adequate patent coverage of new
inventions that may issue as a result of
Government funding of the proposed work;
NOTE: A formal statement of Patent
Agreement among all Group members and
their institutions, as well as a
detailed description of procedures to
be followed for the resolution of
legal problems that may develop,
signed and dated by the
organizational official authorized to
enter into patent arrangements for
each Group member and member
institution, is to be submitted to
Dr. Margaret Johnston, as described
under Section VII, "PATENT COVERAGE."
E. Provide a clear, concise plan in narrative and
diagrammatic form that depicts the
interrelationships among the members of the
Group and the contribution of each to
fulfillment of Group objectives; provide an
organizational chart of the Group showing the
name, organization, and scientific discipline
of the Principal Investigator and Project
Leaders; provide an organizational chart for
each laboratory project within the Group
showing relationships among the key personnel;
F. Provide a plan to assure the maintenance of
close collaboration and effective
communication among members of the Group that
will include letters of commitment to this
plan and a letter accepting the assistance of
the Scientific Coordinator, defined under Section VIII,
"TERMS OF AWARDS".
G. Demonstrate that each component research
project contributes to the attainment of the
Group's objectives and that each has available
the professional and technical personnel to
permit efficient and successful conduct of the
proposed research; show that total personnel
of the Group are sufficient in quality and
quantity to assure successful conduct of the
proposed research; and
NOTE: Other activities which are essential
to maintaining or achieving the
objectives of the stated research
projects (e.g., large-scale
production of reagents, animal
maintenance) should be included as
subcontracts under the budget for
core resources.
H. Demonstrate that each component laboratory
project and the Group as a whole have
available the facilities required for conduct
of the proposed research; demonstrate that
appropriate biohazard facilities and safety
procedures are in place for activities
involving opportunistic pathogens and
pathogen-producing cell lines as outlined in
The Federal Register, Volume 49, Number 201, Part 2,
Tuesday, October 16, 1984, p. 40556;
include a description of the
Institutional Safety Guidelines and
administrative approval procedures for each
proposed laboratory project.
X. REVIEW METHOD AND PERR REVIEW CRITERIA
APPLICATIONS NOT RECEIVED AS A SINGLE
PACKAGE FROM THE PRINCIPAL INVESTIGATOR AND THAT DO
NOT CONFORM TO THE INSTRUCTIONS CONTAINED IN PHS 398
(rev. 10/88 or 9/89) APPLICATION KIT WILL BE JUDGED
NON-RESPONSIVE AND WILL BE RETURNED TO THE APPLICANT.
Applications will be reviewed by NIAID staff to
determine administrative and programmatic
responsiveness to this RFA; those judged to be non-
responsive will be returned to the applicant without
review.
Those applications that are complete and responsive
may be subjected to a triage by an NIAID peer review
group to determine their scientific merit relative to
the other applications received in response to this
RFA. The NIAID will withdraw from competition those
applications judged to be noncompetitive for award and
will notify the applicant Principal Investigator and
institutional business official.
Those applications judged to be competitive for award
will be further reviewed for scientific and technical
merit by a Review Committee convened by the Division
of Extramural Activities, NIAID, during February 1991.
The final level of review will be provided by the
National Advisory Allergy and Infectious Diseases
Council.
REVIEW PROCEDURES AND CRITERIA
Applications will be reviewed in the AIDS Review
Section, NIAID, by an appropriate committee. The
application must be directed towards the attainment of
the stated programmatic goals (see Section VI,
"RESEARCH GOALS AND SCOPE"). The following factors
will be considered in the scientific and technical
review of the application:
A. Relevance of applicant's (Group) objectives to
the discovery of new entities and strategies
for the treatment of OIs in AIDS patients;
B. Scientific and technical significance,
originality, and uniqueness of proposed
research;
C. Scientific merit of approaches to realization
of objectives;
D. Relevance and compatibility of Group's
objectives with NIAID Program's missions and
directions;
E. Specific competencies of the Principal
Investigator and Project Leaders to conduct
the proposed work: research experience,
commitment, and time availability of Principal
Investigator, Project Leaders, and other key
personnel. While there is no maximum percent
effort set, it is anticipated that, due to the
complexity and time required to maintain a
well-coordinated and productive research
effort, a 20% effort by the Principal
Investigator and each Project Leader should be
devoted to the study, unless there is
compelling evidence to the contrary.
F. Likelihood that new potential therapy will be
identified during the course of the proposed
study;
G. Technical merit of proposed methods for
producing or obtaining test materials and for
their evaluation;
H. Technical sufficiency of methods for
evaluation of new discoveries, laboratory test
systems, models, etc.;
I. Administrative experience and competence of the
Principal Investigator in the development,
implementation, and management of
comprehensive research programs;
J. Plans for effective intra-Group communication
and for assuring Group cohesiveness;
K. Adequacy of existing physical facilities and
resources of the Principal Investigator and
Project Leaders including biohazard
containment facilities as stipulated in
Section IX, "MINIMUM REQUIREMENTS FOR
APPLICATION," Part H;
L. Documented commitment of institutions
represented by Group members; documented
capability of Principal Investigator's
institution to serve as Central Operations
Office for the Group;
M. Commitment to accept the assistance of NIAID
staff in accordance with the guidelines
outlined under Section VIII, "TERMS OF AWARD;
NATURE OF PARTICIPATION OF NIAID STAFF;"
N. Mechanism for selecting and replacing key
professional or technical personnel using the
framework of the RFA;
O. Ability of the Principal Investigator and
Project Leaders to devote adequate time to the
effective conduct of the study;
P. Conformance to "MINIMUM REQUIREMENTS FOR
APPLICATION" (Section IX);
Q. Reasonableness of cost.
XI. METHOD OF APPLYING
Before preparing an application, the prospective
applicant should carefully read the NIAID Information
Brochure on Program Project and Center Grants.
The Information
Brochure may be obtained from:
Ms. Barbara Gunter
Developmental Therapeutics Branch
Division of AIDS
National Institute of Allergy
and Infectious Diseases
6003 Executive Boulevard, Room 243
Bethesda, MD 20892
Telephone: (301) 496-8197
The Information Brochure contains special instructions
for preparing multi-project applications, review
procedures, review criteria, and other important
information. It is important to follow the
instructions for preparing the application as outlined
in the Information Brochure. Failure to do so may
result in an application with insufficient information
for appropriate scientific review. Questions
regarding instructions in the brochure should be
directed to Dr. Hortencia Hornbeak (301) 496-0123.
Questions regarding responsiveness to the RFA should
be directed to Dr. Margaret Johnston (301) 496-8197.
o Receipt Date
The deadline for receipt of applications is
December 10, 1990. Applications received
after this date will be considered as not
responsive to this RFA and will be returned
without review.
o General
1. The regular research grant application
forms PHS-398 (rev. 10/88 or 9/89) are
available at most institutional business
offices or from:
Office of Grants Inquiry
Room 449 Westwood Building
Division of Research Grants
National Institutes of Health
9000 Rockville Pike
Bethesda, MD 20892
2. Submit a signed, typewritten original of
the application, including the Checklist,
and six signed, exact, single-sided
photocopies, in one package to:
Division of Research Grants
Westwood Building, Room 240
Bethesda, MD 20892**
The RFA label available in the form PHS-398
(rev. 10/88 or 9/89) must be affixed to the
bottom of the face page of the original signed
application. Failure to use this label could
result in delayed processing of the
application such that it may not reach the
committee in time for review.
3. TO ASSURE THE IDENTIFICATION OF YOUR
APPLICATION WITH THIS RFA:
a. The application form must have
"NATIONAL COOPERATIVE DRUG DISCOVERY
GROUPS FOR THE TREATMENT OF ACQUIRED
IMMUNE DEFICIENCY SYNDROME:
OPPORTUNISTIC INFECTIONS" (RFA AI-90-
10) typed on item 2 of the face
page of the application form; and
4. Prominently label the application
according to one of the following
categories in the opening sentence of the
research plan:
a. THIS IS A COMPREHENSIVE NCDDG
APPLICATION
b. THIS NCDDG APPLICATION IS IMMUNOLOGIC
ONLY
c. THIS NCDDG APPLICATION IS SYNTHETIC
ONLY
d. THIS NCDDG APPLICATION IS BIOLOGICAL
ONLY
e. THIS NCDDG APPLICATION IS A
COMBINATION (two categories from b,
c, and d):
This facilitates assignment of the
application to reviewers with appropriate
expertise.
5. SUBMIT 17 EXACT COPIES OF YOUR APPLICATION
DIRECTLY TO Dr. Hortencia Hornbeak:
Dr. Hortencia Hornbeak
Deputy Chief, Review Branch
Program Project and Review Branch
National Institute of Allergy
and Infectious Diseases
Westwood Building, Room 3A05
Bethesda, MD 20892
Telephone: (301) 496-0123
o Organization of Application and Suggested
Modifications of Form PHS-398 (rev. 10/88 or
9/89)
This RFA requires the submission of a single
application for the proposed NCDDG.
Because of
the multi-institutional nature of an NCDDG and
the special requirements in this RFA,
additional instructions regarding format are
contained in the NIAID Program and Project
Information Brochure.
The special requirements of this RFA will also
necessitate the following modification. The
Introductory Section should apply to the
proposed NCDDG as a whole with respect to
goals, objectives, and overall research plan.
The Introductory Section, not to exceed two
pages, should contain any additional
information about 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 Central
Operations Office.
In addition, the Introductory Section must
include the following elements to be
considered responsive to minimum requirements
(See Section IX, "MINIMUM REQUIREMENTS FOR
APPLICATION", of this RFA):
1. the name of a single Principal
Investigator in accordance with Section
IX, Part A;
2. the name of the single applicant
organization that will provide and operate
the Central Operations Office in
accordance with Section IX, Part B;
3. a statement assuring adequate patent
coverage of new inventions that may issue
as a result of Government funding in
accordance with Section IX, Part D;
4. a statement of acceptance of the
provisions of Section VIII, "TERMS OF
AWARD: AWARDEE RIGHTS AND
RESPONSIBILITIES; NATURE OF PARTICIPATION
OF NIAID STAFF;"
5. a description of the inter-relationships
among members of the Group and
organizational charts in accordance with
Section IX, Part E; and
6. a plan to assure maintenance of close
collaboration and effective communication
among members of the Group in accordance
with Section IX, Part F.
XII. INQUIRIES
Inquiries of the program aspects of this RFA may be
addressed to Dr. Margaret Johnston (see LETTER OF INTENT).
Inquiries regarding matters pertaining to the review
of this application should be addressed to Dr.
Hornbeak. Inquiries regarding fiscal matters may be
addressed to Mr. Thompson.
Mr. Gary Thompson
Chief, Grants Management Branch
Westwood Building, Room 726
NIAID, NIH
Bethesda, MD 20892
Telephone: (301) 496-7231
Hortencia Hornbeak, Ph.D.
Deputy Chief, Review Branch
Westwood Building, Room 3A05
NIAID, NIH
Bethesda, MD 20892
Telephone: (301) 496-0123
XIII. OTHER
A separate request for Applications for the
National Cooperative Drug Discovery Groups for
the Treatment of HIV Infection (RFA
AI-90-09) has been issued. To receive a copy,
please contact Ms. Barbara Gunter (see Section
XI, "METHOD OF APPLYING").