kristoff@GENBANK.BIO.NET (Dave Kristofferson) (03/01/91)
$$XID RFA LM9101 LM-91-01 P1O1 *****************************************
MEDICAL INFORMATICS RESEARCH TRAINING
RFA: LM-91-01
P.T. 22; K.W. 1004017, 1004000, 0720005, 0710030
National Library of Medicine
Letter of Intent Receipt Date: May 1, 1991
Application Receipt Date: June 10, 1991
PURPOSE
The National Library of Medicine (NLM) invites training grant
applications in a single competition for predoctoral and
postdoctoral research training in medical informatics.
Applications may be for the creation of new training centers
or for the renewal of existing NLM-supported training
programs. Such training will help meet a growing need for
qualified, talented investigators, well prepared to address
information problems in health care, health professional
education, and biomedical research. These investigators
will contribute to the growth of science by their studies of
knowledge management and by advancing the frontiers of the
computer sciences for acquiring, organizing, retrieving, and
utilizing health knowledge. The expectation is that
trainees will become able, cross-disciplinary informatics
specialists.
BACKGROUND
Medical informatics goes beyond the use of the computer as a
computational tool and extends into the process of knowledge
representation, acquisition, storage, retrieval, and
manipulation largely to support reasoning and decision-
making.
OBJECTIVES
Acceptable applications must clearly indicate that the
primary intent of the program is preparation for an academic
career in Medical Informatics. Applications must describe
the process by which trainees will become familiar with the
many relevant disciplines. To prepare trainees for research
careers in a demanding research environment, the sponsorship
of a research-oriented, academic health sciences institution
is critical. It is expected that the core of training will
emphasize the synthesis, organization, retrieval, and
effective management of knowledge. The curricula should be
inter-disciplinary by including topics in medicine and the biological
sciences, the cognitive sciences, information science, and computer
science. Training sites must offer an excellent setting for instruction
in important health computer science research programs, and
opportunities for meaningful trainee involvement in such research.
In addition to the general goal of assisting in the
education of persons to take academic positions to
conduct research and teach medical informatics, several more
specialized additions to the training programs are likely to
become available during the next few years to enhance
research training grants approved in the FY 1991 competition.
Consequently, NLM invites applicant institutions to include
their plans for such possible enhancements within the
application. Some potential enhancement areas (described in
the following paragraphs) are high performance computing and
communication, biotechnology, cancer, and information
systems. Dental informatics is another area for which
additional training slots may become available in the
future.
High performance computers and high speed computer networks
are key technologies for modern science. Applicants should
be aware that the President's Office of Science and
Technology Policy has proposed a multi-agency High
Performance Computing and Communication Initiative (HPCC).
NLM, representing NIH, is included in the HPCC as the
biomedical component. These activities will include creation
and transmission of digital electronic images, linking of
academic health centers via the future high performance
communication networks, and development of advanced methods
of retrieving biomedical information (as well as molecular
biology computing, and training in informatics). Applicants
for NLM training program support are encouraged to indicate
their experience in any of these Enhancement Areas, and to
indicate those areas (if any) in which they may plan to
offer training experience, or in which they could in the
future accept candidates for training.
Increases in funding support in
these areas might take the form of supplements to training
grants and/or the availability of individual fellowships in
one or more of the Enhancement Areas.
The recent establishment within NLM of the National Center
for Biotechnology Information intensifies the Library's
interest and responsibilities in this special area of
informatics. The appearance of new experimental methods has
greatly increased the rate at which data are accumulating
about the molecular control of life processes. Because of
their enormous size and subtle complexity, the vast data
accumulations can only be analyzed and compared by
sophisticated computer methodologies. Applicants are urged
to include training in biotechnology informatics in their
proposed curriculum, if such training is feasible and
appropriate for the institution.
The National Cancer Institute (NCI) plans to make available
up to $100,000 through this RFA. These funds would support
four (4) trainees whose projects deal with the application
of medical informatics approaches to the problems of cancer
diagnosis and therapy. For support under this special
training track, sponsors/preceptors must request
consideration for funding by NCI and must describe how
their projects will be of benefit to the field of cancer (as
described below). The sponsoring institution must have a
strong department in the radiological sciences and indicate
its awareness of and commitment to the application of
medical informatics to radiological research that is
relevant to the diagnosis and treatment of cancer.
The purpose of this special training track is to stimulate
qualified candidates to apply for post-doctoral Medical
Informatics fellowships in areas of Radiological Sciences
that deal directly with cancer-related topics. When
possible, the curricula should be interdisciplinary
involving radiation oncology, diagnostic radiology,
cognitive sciences, information sciences and/or computer
science.
Training grant applications which include sponsors/
preceptors who are requesting support for cancer-related
projects will be subjected to the same peer review process
as all other applications submitted in response to this RFA,
and grants selected for an award will be administered by the
NLM. Prospective applicants who have an interest in the
special training track of the National Cancer Institute
should declare their interest and focus that part of the
application on areas in the Radiological Sciences that
support problem-solving in cancer-related topics. Support
of training slots by the NCI will be based on the Initial
Review Group's recommendation and percentile score,
relevance of the proposed project to the radiological
problems that relate to the diagnosis and treatment of the
cancer patient, program interests and the availability of
funds.
The preparation of competent scientists remains the primary
goal of the training program. However, NLM recognizes that
informatics specialists are often called upon for assistance
in addressing information needs of a health center, and
strongly encourages program directors to provide trainees
with some exposure to the problems of managing and
integrating academic information systems. Such training may
be of particular interest to students enrolled in an
Master of Library Science program.
Institutions wishing to include the research experience
gained by a trainee toward the research requirements of
Board certification may do so at their discretion.
Proposals designed as preparation for certification in toto
in medical specialties will not be acceptable.
MECHANISM OF SUPPORT
NLM plans to make available approximately $3 million for
this program in FY 1992. It is expected that six to ten
training grants will be awarded; however, actual award of
grants pursuant to this RFA is necessarily contingent upon
receipt of funds appropriated for this purpose. The
specific number will also depend upon the merit and scope of
applications received as well as the availability of funds.
These awards are authorized by the Medical Library
Assistance Act and are not part of the National Research
Service Awards Program of the Public Health Service.
However, the policies and requirements of the NLM program
are similar to Public Health Service National Research
Service Awards.
Trainees must be citizens or non-citizen nationals of the
United States or have been lawfully admitted for permanent
residence at the time of appointment. Individuals on
temporary or student visas are not eligible.
Predoctoral students who have been accepted as candidates
for the doctor of philosophy of science or equivalent degree
at their institutions may be appointed as predoctoral
trainees for a period not to exceed three years.
Individuals who wish to interrupt their medical, veterinary,
dental, or other professional school studies for a year or
more to engage in full-time research training before
completing their professional degrees are eligible. Also
eligible are students enrolled in MLS programs.
The current stipened level for predoctoral individuals at
all levels of experience is $8,800 per annum. There is no
payback requirement.
Postdoctoral individuals must have received, as of the
beginning date of appointment, a Ph.D., M.D., D.O., D.D.S.,
D.V.M., O.D., D.P.M., Sc.D., Eng.D., Dr.P.H., D.N.Sc., or
equivalent degree from an accredited domestic or foreign
institution. Certification by an authorized official of the
degree-granting institution that all degree requirements
have been met is acceptable.
The postdoctoral stipend for the first year of support is
determined by the number of years of relevant postdoctoral
experience at the time of appointment. Relevant experience
may include research experience (including industrial),
teaching, internship, residency, or other time spent in
full-time studies in a health-related field beyond that of
the qualifying doctoral degree. The stipend for each
additional year of support is the next level on the stipend
structure. Current postdoctoral stipends are as follows:
Years of Relevant Experience Stipend
0 $18,600
1 19,700
2 25,600
3 26,900
4 28,200
5 29,500
6 30,800
7 or more 32,300
Stipends may be supplemented by an institution from
non-Federal funds. No Federal funds may be used for stipend
supplementation unless specifically authorized under the
terms of the program from which funds are derived. Under no
circumstances may the conditions of stipend supplementation
detract from or prolong the training.
Tuition, fees, and medical insurance are allowable trainee
costs if such charges are required of all persons in a
similar training status at the institution, without regard
to their source of support. Tuition at the postdoctoral
level is limited to that required for specific courses in
support of the approved training program. Costs of trainee
travel, including attendance at scientific meetings that
the institution determines to be necessary to the
individual's training, may be requested.
Institutional costs of up to $1,500 per year per predoctoral
trainee and up to $2,500 per year per postdoctoral trainee
may be requested to defray the costs of training-related
expenses such as staff salaries, consultant costs,
equipment, research supplies, staff travel, and other
expenses. The availability of funds may modify the maximum
levels of institutional costs awarded. An indirect cost
allowance based on 8% of total allowable direct costs or
actual indirect costs, whichever is less, may be requested.
In their proposed budgets, applicants should request trainee
travel funds for a two-day meeting each year, most likely to
be held at the NLM in Bethesda.
The purpose of these meetings will be to exchange
information among trainees, program directors, NLM program
staff, and other selected participants.
NLM recognizes that the technological fields upon which
medical informatics is based are advancing at a rapid rate.
Special hardware, new software, and access to centralized
databases and information sources continue to evolve, and
the trainees must be given the opportunity to work with the
latest equipment. The necessity for this support is a
unique one occasioned by the nature of the field of medical
informatics and the type of training required. The budget
requested may not exceed $6,000 per trainee and must relate
reasonably to the provision of computer and information
support.
Short-term traineeships are available for students in
medical or other professional schools of the health
sciences. Such training is intended to give a limited
number of selected students summer or "off-quarter"
opportunities for involvement in research so that they might
consider medical informatics as a career option. Students
selected should be encouraged to have two or more short-term
training appointments during the period of their
professional school years, thus giving an individual student
multiple periods of exposure to research training. Senior
students would not normally be eligible for a first
appointment to a short-term traineeship; exceptions may be
requested from NLM. The stipend level for such short-term
traineeships is at an $8,800 annual rate.
Recognizing that training programs of this nature require
reasonably long-term continuity, NLM is prepared to approve
awards for five-year periods. At an appropriate time, the
availability of renewal support for these training program
grants will be announced.
REVIEW PROCEDURES AND CRITERIA
Prior to initial scientific merit review, a triage mechanism
may be employed to screen out applications that are clearly
noncompetitive.
Applications will be evaluated initially by an NLM peer
review committee for scientific and technical merit. A
second review will be conducted by the Board of Regents of
the National Library of Medicine.
The training programs should demonstrate an ability to
recruit persons with high potential for academic research
careers and for continuing in the field of Medical
Informatics. The trainees should be recognized as potential
scientific leaders, able to build new departments and
strengthen existing ones. Although postdoctoral candidates
for training should be clearly destined for health research
careers in this field, their doctorates may have been earned
in any appropriate field of endeavor, such as medicine,
dentistry, nursing, computer science, engineering or any of
the biological sciences. Sites should be academic medical
centers; however, consortium training arrangements with
other graduate schools and institutions are encouraged.
The NIH and NLM policy is to promote broader and systematic
efforts to recruit women and individuals from minority
groups who are currently underrepresented in biomedical and
behavioral research. Initial review groups will address the
following points:
o The applicant's specific plans for the recruitment of
individuals from underrepresented groups.
o The applicant's past record in selecting representatives
from underrepresented groups and in training them for
research programs.
Accomplishments in these areas will ensure that the
underrepresented are progressively better represented in
biomedical and behavioral research. Applications which do
not have satisfactory plans for the recruitment of trainees
from such groups will not be funded.
Effective July 1, 1990, all competing institutional training
grant applications must include a description of the formal
or informal activities related to instruction in the
responsible conduct of research that will be incorporated
into the proposed research training program. A statement of
NIH policy on instructions in the responsible conduct of
research appeared in the NIH Guide for Grants and Contracts
on December 22, 1989 (Vol. 18, No. 45., Page 1) and an
update of this announcement appeared in the NIH Guide for
Grants and Contracts on August 17, 1990.
Review criteria will include the curricular offerings and
participation in or involvement with on-going research in
the field of medical informatics. Program directors and
their colleagues must demonstrate success in obtaining
research support. Reviewers will assess the strength of
linkages with other relevant disciplines in medicine and the
computer sciences. These linkages may be forged within the
institution or with others, possibly in a consortium. The
positive sponsorship and contribution of resources by the
applicant institution will be significant to reviewers.
Institutional prospects for growth of the computer sciences,
including research career opportunities, will also be
significant.
LETTER OF INTENT:
Prospective applicants are asked to submit by May 1, 1991, a
letter of intent that includes a descriptive title, the name and
The letter of intent is requested in order to
address of the Principal Investigator, the names and addresses of
any other key investigators, and the names of other participating
institutions.
provide an indication of the number and scope of
applications to be reviewed. The letter of intent is not
binding, nor is it a requirement for submission of an
application. The letter of intent should be sent to:
Roger W. Dahlen, Ph.D.
Chief, Biomedical Information
Support Branch
Extramural Programs
National Library of Medicine
8600 Rockville Pike
Building 38A, Room 5S522
Bethesda, MD 20894
Telephone: (301) 496-4221
FAX: (301) 402-0421
METHOD OF APPLYING
Applications for these training awards must be submitted
on PHS 398 (rev. 10/88). Forms may be obtained from institutional
application control offices and upon request from:
Office of Grants Inquiries
Division of Research Grants
National Institutes of Health
Westwood Building, Room 448
Bethesda, MD 20892
Telephone: (301) 496-7441
Applicants should clearly identify the application as a response to this
RFA by entering the title, "Medical Informatics Research Training," and
the RFA number on line 2 of the face page.
The mailing
label available in the 10/88 revision (reprinted 9/89) of the
form 398 should be used and the RFA label should be stapled
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.
Send or deliver the completed application and six (6)
signed, exact photocopies to:
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892
Applications must be received by June 10, 1991. The initial
review group will meet in July/August, and the Board of
Regents of the NLM will conduct a
final review in September 1991. NLM will notify successful
applicants about an intention to award shortly after the
Board meeting. Although notification of intent to award
cannot assure an award, only those so notified will be
considered for funding. It is intended to issue awards with
a July 1, 1992 begin date. In the administration of awards,
the policies and requirements of the grant programs of the
Public Health Service apply.
Inquiries about the program and this announcement may be
directed to program officials at:
Biomedical Information Support Branch
Extramural Programs
National Library of Medicine
Bethesda, MD 20894
Telephone: (301) 496-4221
For fiscal and administrative matters, contact:
Ruth Bortz
National Library of Medicine
8600 Rockville Pike
Building 38A, Room 5S522
Bethesda, MD 20892
Telephone: (301) 496-4253
This program is described in the Catalog of Federal Domestic
Assistance, Medical Library Assistance, 13.879. Grants will
be awarded under the authority of the Public Health Service
Act, Section 472 (42 USC 286b-3) and administered under PHS
grant policies and Federal Regulations, most specifically at
42 CFR Part 52 and 45 CFR Part 74. This program is not
subject to review by a Health Systems Agency nor to the
requirements of OMB Circular A-95.
$$XID RFA AG9109 AG-91-09 P1O1 *****************************************
REQUEST FOR PROGRAM PROJECT APPLICATIONS
DRUG DISCOVERY GROUPS FOR THE TREATMENT OF COGNITIVE
IMPAIRMENT ASSOCIATED WITH ALZHEIMER'S DISEASE
RFA: AG-91-09
P.T. 34; K.W. 0715180, 0740020, 0755025
National Institute on Aging
Application Receipt Date: May 21, 1991
Letter of Intent Receipt Date: April 1, 1991
The National Institute on Aging (NIA) invites program project
applications (P01) for the establishment of Drug Discovery
Groups for the Treatment of Cognitive Impairment Associated
With Alzheimer's Disease.
There are no present plans to reissue this Request for
Applications (RFA) at any future time. The NIA intends to
invite competitive renewal applications upon expiration of
the initial funding period, contingent on the continued
availability of funds for this purpose.
I. BACKGROUND
Alzheimer's disease (AD) is one of the most persistent and
devastating dementing disorders of old age, because it
eventually leads to a complete loss of memory and of the
ability to function independently. It is estimated that
about four million people in the United States have AD in its
various stages at an estimated cost to society of $90 billion
per year, and it is projected that 14 million people could be
victims of Alzheimer's disease by the middle of the next
century. The disease presents enormous problems not only to
the affected individual but also to the families and raises
many complex social and economic issues for the country.
AD provides a complex neurochemical puzzle and present
efforts to treat it have not yet produced any reliable
compounds. The U.S. Congress has recognized this problem,
and as part of the FY91 appropriation for NIA, has mandated
that NIA "explore new treatment and management methods,
including testing promising drugs, such as nerve growth
factor and acetylcarnitine, that could safely and effectively
slow or reverse the symptoms of Alzheimer's disease."
The NIA has responded to the Congressional language and the
need for a broader research effort in two ways. The goal of
this RFA is to promote the development of a broader range of
potentially efficacious compounds beyond the current examples
of cholinesterase inhibitors, cholinergic agonists, nerve
growth factor, and acetylcarnitine. The goal of a companion
RFA (AG-91-10) is to assess the efficacy of a large number of
compounds in short-term clinical studies as a preliminary
measure to fully developed long-term clinical trials.
The etiology of AD is not known, and the pathobiological
processes that underlie the steady progression of the
clinical course of this disease are not well understood. It
is clear, however, that mechanisms of cell to cell
communication are disrupted. These involve several different
types of neurotransmitter, neuropeptide, and neuromodulator
systems, neurochemical processes, and elements of the
oxidative and cellular energy metabolism processes. The
hallmark of the disease involves progressive cell
dysfunction, cell loss, and the accumulation of a wide
variety of abnormal protein and cytoskeletal abnormalities.
At present it is not known when and how the degenerative
process begins; for example, it is not clear whether
fragments of amyloid protein initiate the degenerative
process or the formation and accumulation of the protein is
the end result of gradual cell atrophy and death initiated by
some other agent or process.
At present there are no generally safe and effective
treatments for AD. The few agents that are available have
demonstrated only modest effects in slowing the rate of
progression of the cognitive decline for short periods in
subsets of patients. The majority of the compounds
considered candidate drugs have been developed primarily for
other disorders and have generally been designed to modify
the synthesis, release, or degradation of neurotransmitters.
Most of the agents have been targeted towards the cholinergic
system which is an especially vulnerable neural population in
AD and cognitive function.
The NIA currently supports extramural and intramural projects
for the study of the epidemiology, etiology, diagnosis, and
treatment of AD. Notwithstanding these efforts, the
increasing numbers of affected individuals, the unknown
etiology, the emotional, social, and economic costs to the
victims, caregivers, and society, and the fact that there is
no compound which can uniformly slow or reverse the
progression of the disease or ameliorate the symptoms, all
require that the most creative scientific talents in all
relevant scientific disciplines and organizations be
mobilized into groups which will aggressively pursue a
concerted effort to discover compounds and strategies for the
treatment of the disease. Agents are needed which can
ameliorate the symptoms of the disease even for a short time,
because such agents would provide needed relief, however
brief, to the victims and their families.
II. RESEARCH OBJECTIVES AND SCOPE
The objective of this solicitation is to stimulate multi-
center multi-disciplinary preclinical research in the design,
development and testing of novel compounds aimed at slowing,
halting, or, if possible, reversing the progressive decline
in cognitive function in Alzheimer's disease victims. This
initiative is intended to stimulate basic research and
development efforts which go beyond those already underway or
likely to be undertaken by pharmaceutical firms in the
foreseeable future. The goal of this effort is not to
duplicate or compete with pharmaceutical companies but to
encourage, complement, and accelerate the process of
discovering new, innovative, and effective treatments for
cognitive impairment in Alzheimer's disease.
The development of compounds for ameliorating, modifying, or
improving potential aberrations in the neuronal signal
transduction pathway is encouraged. These treatments should
be designed to ameliorate fundamental processes of the neural
dysfunction and cell death associated with the disease by
targeting aspects of the signal transduction pathway; e.g.
membrane, second and third messenger, phosphorylation, and
signal amplification stages. To the extent it is possible
and practical, this initiative would encourage cooperation
and collaboration with scientists associated with
pharmaceutical and biotechnology companies.
The drug development group should include the perspectives,
skills, and knowledge not only of neuropharmacologists but
also of medicinal chemists, membrane biophysicists, protein
chemists, molecular biologists, neurophysiologists, and
behavioral pharmacologists.
Research directed toward drug discovery utilizing one or more
of the following examples or other novel approaches will be
considered responsive to this RFA.
1. Design and synthesis of compounds directed toward
altering, modifying, or regulating the following aspects of
signal transduction mechanisms:
o Membrane and cytoskeletal composition, structure and
function;
o Protein phosphorylation and dephosphorylation;
o Channel function and structure;
o Second and/or third messengers;
o Gene expression or transcription;
o Neurotrophic and growth promoting factors;
o Mitochondrial function and cellular energy metabolism;
o Formation of abnormal proteins;
o Synthesis and degradation of proteins;
o Ionic transport.
2. The isolation, identification and characterization of
promising naturally occurring products or synthetic chemical
compounds.
3. Development of delivery systems to target compounds to the
brain.
The above-mentioned areas of investigations are
representative and not meant to be inclusive. Investigators
are encouraged to explore other avenues to identify potential
therapeutic agents.
Many single institutions may not have either the critical
mass of all of the talents or the ancillary resources needed
to translate leads from basic studies into new entities and
strategies for AD treatment. Units in which these research
talents and resources are combined are termed "DRUG DISCOVERY
GROUPS FOR ALZHEIMER'S DISEASE" (DDG-AD). They are envisioned
as having the capacity to generate new approaches and
strategies for the treatment of AD and to rapidly translate
their concepts into potentially effective treatment. Results
from the research proposed should be used to identify and
develop information for long term planning of potential
therapeutic approaches or to recommend new potential
treatments worthy of further development to clinical trial.
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 are required to
attain the Group's objectives.
Large-scale random screening of compounds will not be
supported under this RFA.
Extensive studies required for the clinical development of
identified potential treatments are beyond the scope of this
RFA. However, funds should be budgeted in the later years of
this project (years 3-5) for investigating underlying
mechanisms of toxicity, including studies of pharmacokinetics
and pharmacodynamics, of promising compounds to begin
preparing the data necessary to support initial human
testing.
III. MECHANISM OF SUPPORT
A. Awards will be made as PROGRAM PROJECTS. 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 treatment and to facilitate
their subsequent development to clinical trial. However, if
employees of commercial organizations are involved, an
agreement must be worked out with the Principal Investigator
and other participants with respect to proprietary rights and
publications before the individual begins work on the
project.
B. NIA has set aside $2.25 million in total costs 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 awards is anticipated. The dollar
value of each DDG-AD award is limited to $750,000 in total
costs. The starting date for the initial annual period will
be on or before September 30, 1991.
C. Awards will be made to successfully competing applicant
institutions. Support of all Group activities will be
coordinated through a Central Operations Office located
within the applicant organization. An award will be made only
to the Principal Investigator's institution.
D. All policies and requirements that govern the grant
program of the U.S. Public Health Service and the NIH apply.
E. Although this program is provided for in the financial
plans of NIA, the award of Program Projects pursuant to this
RFA is also contingent upon the continuing availability of
funds for this purpose.
IV. DEFINITIONS
CORE COMPONENT - Laboratory facilities for equipment and/or
services that shall be shared by two or more projects of the
DDG-AD. Examples of core components are neurochemical
laboratories, animal model development or efficacy testing,
and scale-up synthesis of drugs (ten grams or less). The core
can be defined as any facility with established techniques
and assays which performs a service function or results in an
economy of effort and savings in the overall costs of the
DDG-AD.
DISCOVERY - The term "discovery" is used explicitly to limit
activities of the DDG-AD 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.
DRUG DISCOVERY GROUP FOR ALZHEIMER'S DISEASE (DDG-AD) - In
this RFA the terms DRUG DISCOVERY GROUP, DDG-AD, 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 AD. Groups must consist
of at least three independent Projects conducted by at least
three separate and independent investigators. A CORE
COMPONENT cannot be used toward fulfillment of the three
Projects requirement.
NEW DRUG - In the context of the DDG-AD 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
cognitive impairment in AD patients.
PRINCIPAL INVESTIGATOR - The person who assembles the DDG-AD,
assembles a single application with the information provided
by the Project Leaders, submits the application in response
to this RFA, and is responsible for the performance of the
Group as a whole and each of the Project Leaders. The
Principal Investigator must 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 DDG-AD.
SCIENTIFIC ADVISORS PANEL - A panel, comprised of 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 proposed
composition of the Panel will be provided in the
Noncompetitive Renewal Application at the completion of year
one of funding. The Panel will provide a comprehensive review
of the Group's activity in years two through five 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
DDG-AD Program; and recommendations for new directions, as
appropriate.
V. COMPOSITION OF A DDG-AD
A. The DDG-AD 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
that are appropriate to the realization of Group objectives
(e.g., neurochemistry, neuropharmacology, molecular
neurobiology, medicinal chemistry, organic chemistry,
behavioral pharmacology, etc.). Interdisciplinary projects
are encouraged;
3. (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 an
Administrative Core that would provide the administrative,
purchasing, and secretarial services. Items described above
are to be requested and funded only if they are classified as
direct costs at the applicant institution.
4. A Scientific Advisors Panel to be designated at
the end of year one 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. Members of
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, must direct 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 a DDG-AD should be the
mobilization of maximum intellectual strength and the ability
to carry out the proposed research.
D. A DDG-AD may have more than one project from the same
institution. However, the varied talents and commitment
required for effective drug discovery may not be present in
one institution, and the Project Leaders within a Group could
be from more than one institution.
E. A minimum of three 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.
F. In forming Groups, Principal Investigators should remain
cognizant of the need for communication, including regular
meetings of the members, and funds should be budgeted for
these meetings. Additionally, funds should be budgeted for
the investigators to attend an annual meeting of all the DDG-
AD's at which all Principal Investigators and Project Leaders
will present findings in symposium format. 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 if the
applicant proposes laboratory projects in foreign countries.
G. A DDG-AD 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-AD therapies. However, if employees of
commercial organizations are involved, an agreement must be
worked out with the Principal Investigator and other
participants with respect to proprietary rights and
publications before the individual begins work on the
project.
VI. RESEARCH GOALS AND SCOPE
A. The overall goals of the DDG-AD are the conceptualization,
discovery, and preclinical development and testing of
compounds which will lead to the selection of potential
therapies designed to effectively treat the cognitive
impairment in individuals suffering from AD.
B. Applications for a DDG-AD should stress innovative
approaches to the discovery of effective therapies to treat
AD and should emphasize the following:
1. specific objectives of the proposed DDG-AD;
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 NIA Program's missions and directions as
stated in this RFA.
VII. PATENT COVERAGE
Since the discovery of agents active against cognitive
impairment in AD 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. For
successful applicants, the patent agreement among the
institutions comprising the group, signed and dated by the
organizational officials authorized to enter into patent
arrangements for each Group member and member institution,
must be sent to Program Director, Treatment and Management,
Neuroscience and Neuropsychology of Aging Program, National
Institute on Aging, 9000 Rockville Pike, Bldg. 31, room 5C35,
Bethesda, MD 20892 before an award can be made.
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 copy
to Program Director, Treatment and Management, at the above
address.
VIII. MINIMUM REQUIREMENTS FOR APPLICATION
Applicants seeking funding as a DDG-AD must meet the
following requirements:
The application must be from an eligible institution 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 DDG-AD;
C. Provide a statement that the Group plans to assure
adequate patent coverage of new inventions that may issue as
a result of Government funding of the proposed work;
NOTE: For successful applicants, 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 Program Director,
Treatment and Management, as described under Section VII,
"PATENT COVERAGE," before an award will be made.
D. The application must provide a statement that the
applicant institution and any other institutions involved
have written policy guidelines on conflict of interest and
the avoidance thereof as prescribed in the PHS Grants Policy
Statement [DHHS Publication No. (OASH) 90-50,000, revised
October 1, 1990] and 45 CFR Part 74, Sub-part P and 45 CFR
Part 92.36. This is intended to preclude any potential
conflict of interest of investigators regarding relationships
with and holdings in for-profit pharmaceutical,
biotechnology, or venture capital companies. For the
successful applicant, these guidelines must be provided to
NIA staff upon request.
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.
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;
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 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; include a description of
the Institutional Safety Guidelines and administrative
approval procedures for each proposed laboratory project.
I. As indicated above, extensive studies required for the
clinical development of identified potential treatments are
beyond the scope of this RFA. However, funds should be
budgeted in the later years of this project (years 3-5) for
investigating underlying mechanisms of toxicity, including
studies of pharmacokinetics and pharmacodynamics, of
promising compounds to begin preparing the data necessary to
support initial human testing.
IX. REVIEW PROCEDURES AND PEER REVIEW CRITERIA
A. REVIEW PROCEDURES
Applications will be reviewed by NIA staff to determine
administrative and programmatic responsiveness to this RFA;
those judged to be nonresponsive will be returned to the
applicant without review. Those applications that are
complete and responsive may be subjected to a preliminary
review by a subcommittee of the review group to determine
those applications deemed to be competitive. Those
applications judged to be noncompetitive will be
administratively withdrawn and will be returned to the
applicant investigator with an abbreviated summary statement
noting the major deficiencies. Those applications judged to
be competitive will be further reviewed for scientific and
technical merit by a special review committee convened by the
Scientific Review Office, NIA. Following review by an
initial review group, the application will be considered by
the National Advisory Council on Aging.
All applications must be complete in themselves. Since it is
unlikely that site visits will be conducted, each application
should be prepared as if no such visit will occur.
In preparing applications, applicants should follow the
instructions for PHS form 398 (revised 10/88, reprinted 9/89)
and the specific supplemental instructions included in this
RFA. Applicants are urged to have all Institutional Animal
Care and Use Committee (IACUC) approvals complete and
submitted with the application or received within 30 days of
the application receipt deadline or earlier if requested by
the Executive Secretary. It is incumbent upon the applicant
to ensure that the Executive Secretary receives all
clearances by the established deadline or the application
will not be reviewed.
B. REVIEW CRITERIA
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.
1. Relevance of applicant's (Group) objectives to the
discovery of new entities and strategies for the treatment of
cognitive impairment in AD patients;
2. Scientific and technical significance;
3. Likelihood that the proposed approaches will lead to
realization of objectives;
4. Relevance and compatibility of Group's objectives with NIA
Program's missions and directions;
5. 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, at least 20%
effort by the Principal Investigator and each Project Leader
should be devoted to the study, unless there is compelling
evidence to the contrary;
6. Likelihood that new potential therapy will be identified
during the course of the proposed study;
7. Technical sufficiency of methods for evaluation of new
discoveries, laboratory test systems, models, etc.;
8. Administrative experience and competence of the Principal
Investigator in the development, implementation, and
management of comprehensive research programs;
9. Plans for effective intra-group communication and for
assuring Group cohesiveness;
10. Adequacy of existing physical facilities and resources of
the Principal Investigator and Project Leaders;
11. Documented commitment of institutions represented by
Group members; documented capability of Principal
Investigator's institution to serve as Central Operations
Office for the Group;
12. Mechanism for selecting and replacing key professional or
technical personnel using the framework of the RFA;
13. Conformance to "MINIMUM REQUIREMENTS FOR APPLICATION"
(Section VIII);
14. Reasonableness of cost.
X. METHOD OF APPLYING
A. The application must be submitted on the 10/88 revision
(reprinted 9/89) of the form PHS 398. To identify
applications as being responsive to the RFA, check "yes" on
item 2 of page 1 of the application and enter the title:
"NIA:DDG-AD" and the RFA number (AG-91-09). The mailing
label available in the 10/88 revision (reprinted 9/89) of the
form 398 should be used and the RFA label should be stapled
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.
B. Before preparing an application, the prospective
applicant should carefully read the NIA Information Brochure
on Program Project and Center Grants. The Information
Brochure may be obtained from Dr. Neil Buckholtz or the
Chief, SRO at the addresses given below. 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 as well as the specific
supplemental instructions in this RFA. Failure to do so may
result in an application with insufficient information for
appropriate scientific review. Questions regarding
instructions in the brochure or responsiveness to the RFA
should be directed to Dr. Neil Buckholtz.
C. Organization of Application and Suggested Modifications
of Form PHS-398 (revised 10/88, reprinted 9/89).
This RFA requires the submission of a single application for
the proposed DDG-AD. Because of the multi-institutional
nature of an DDG-AD and the special requirements in this RFA,
additional questions regarding format and/or budget can be
directed to Dr. Buckholtz or Mr. Ellis (see below).
The special requirements of this RFA will also necessitate
the following modification. The Introductory Section should
apply to the proposed DDG-AD 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 VIII, "MINIMUM REQUIREMENTS FOR
APPLICATION", of this RFA):
1. the name of a single Principal Investigator in accordance
with Section VIII, Part A;
2. the name of the single applicant organization that will
provide and operate the Central Operations Office in
accordance with Section VIII, 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 VIII, Part C;
4. a statement assuring compliance with written policy
guidelines on conflict of interest in accordance with Section
VIII, Part D;
5. a description of the inter-relationships among members of
the Group and organizational charts in accordance with
Section VIII, Part E; and
7. a plan to assure maintenance of close collaboration and
effective communication among members of the Group in
accordance with Section VIII, Part F.
Although not a prerequisite for applying, potential
applicants are encouraged to submit to Dr. Buckholtz at the
address below a non-binding letter of intent to apply by
April 1, 1991. The letter of intent is not mandatory and
does not influence review or funding decisions, but it will
enable the NIA to plan the review, and will ensure that each
potential applicant receives relevant program information
prior to expending considerable effort in application
preparation.
Applications must be complete and received by May 21, 1991
for a start date on or before September 30, 1991. If
received late, the application will be returned without
review.
Application kits may be secured from institutional offices of
grants and contracts or from:
Office of Grants Inquiries
Division of Research Grants
National Institutes of Health
Westwood Building, Room 449
Bethesda, MD 20892**
Mail the complete application and four copies to:
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892**
To expedite review, two exact copies should be sent to:
Chief, SRO, OEA, NIA, NIH
Building 31, Room 5C12
9000 Rockville Pike
Bethesda, MD 20892
XI. INQUIRIES
Applicants are strongly encouraged to obtain supplemental
information and to discuss their plans with and direct any
other inquiries to:
Neil Buckholtz, Ph.D.
Program Director, Treatment and Management
NNA, NIA, NIH
Building 31, Room 5C35
9000 Rockville Pike
Bethesda, MD 20892
Telephone: (301) 496-9350
FAX: (301) 496-1494
Inquiries regarding matters pertaining to the review of this
application should be addressed to:
Dr. Michael Oxman
Chief, SRO, OEA, NIA, NIH
Building 31, Room 5C12
9000 Rockville Pike
Bethesda, MD 20892
Telephone: (301) 496-9666
Inquiries regarding fiscal matters may be addressed to:
Mr. Joseph Ellis
Grants Management Offiver
National Institute on Aging
Building 31, Room 5C07
Bethesda, MD 20892
**The mailing address given for sending applications to the
Division of Research Grants or contacting program staff in
the Westwood Building is the central mailing address for the
NIH. Applicants who use express mail or a courier service
are advised to follow the carrier's requirements for showing
a street address. The address for the Westwood Building is:
5333 Westbard Avenue, Bethesda, Maryland 20816.
This program is described in the Catalog of Federal Domestic
Assistance No. 93.866, Neuroscience and Neuropsychology of
Aging. Awards will be made under the authority of the Public
Health Service Act, Title III, Section 301 (Public Law
78.410, as amended; 42 USC 241) and administered under PHS
grant policies and Federal Regulations 42 CFR Part 52 and 45
CFR Part 74. This program is not subject to the
intergovernmental review requirements of Executive Order
12372 or Health Systems Agency review.