kristoff@GENBANK.BIO.NET (Dave Kristofferson) (12/14/89)
NIH SMALL INSTRUMENTATION GRANTS PROGRAM
P.T. 34; K.W. 0735000
National Institutes of Health
Application Receipt Date: February 13, 1990
BACKGROUND
In its appropriation for the NIH for Fiscal Year 1987, the Congress included a
total of $16 million to be spent by the respective
Bureaus/Institutes/Divisions (BIDs) for the funding of grants to purchase
small instruments costing between $5,000 and $60,000. This action was in
response to several recent studies of the problem of obsolete biomedical
research instrumentation, indicating that the state of biomedical research
instrumentation had seriously eroded over the last ten years and that this
situation is retarding the progress of biomedical research. The most
significant need identified in these studies is for the relatively low-cost
pieces of equipment in the price range of approximately $5,000 to $60,000.
Vol. 18, No. 44, December 15, 1989 - Page 13
Approximately $16 million will be available for small instrumentation grants
this year.
ELIGIBILITY AND TERMS OF AWARD
Each institution that received support under the Biomedical Research Support
Grant (BRSG) Program in Fiscal Year 1989 and that currently has active NIH
research grants is eligible to apply. Only one application may be submitted
from each eligible institution or organizational component. Each institution
may establish its own procedures for identifying equipment requests to be
included in its application.
The small instrumentation award will be restricted to the purchase of
equipment costing between $5,000 and $60,000. Awards will be made on or
before September 30, 1990. The amount of the award will be based upon a
percentage of the institution's Biomedical Research Support Grant award for
Fiscal Year 1989 or $5,000, whichever is greater. Specific funding decisions
will depend on available BID appropriations as well as the appropriateness of
the request. Institutions will be notified of the maximum amount for which
they may apply.
METHOD OF APPLYING
Letters of instruction to eligible institutions will be mailed on or about
December 1, 1989.
Completed applications must be received by February 13, 1990.
Investigators interested in participating in their institution's application
must contact the institution's Biomedical Research Support Grant Program
Director. Institutional officials who expect to be involved in preparing an
application are requested to review the letter of instructions prior to
contacting NIH.
**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 NATIONAL INSTITUTES OF HEALTH. 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
Vol. 18, No. 44, December 15, 1989 - Page 14
FULL TEXT OF RFAs FOR ONLINE ACCESS
DEVELOPMENT OF NONMAMMALIAN MODELS FOR BIOMEDICAL RESEARCH
RFA RR-90-01
P.T. 34; K.W. 0755020, 0780015, 0780020
Division of Research Resources
Letter of Intent Receipt Date: February 1, 1990
Application Receipt Date: April 4, 1990
PURPOSE
The Biological Models and Materials Resources Program
(BMMRP) of the Division of Research Resources (DRR) is
issuing this Request for Applications (RFA) for the
development of nonmammalian models, in particular, lower
organisms (such as fishes, invertebrates, and
microorganisms), in vitro (cell and tissue culture) systems,
and nonbiological models (such as mathematical and computer
simulations) for biomedical research.
BACKGROUND
The BMMRP has recently been given program status in DRR to
provide for the development and support of nonmammalian
models, such as cell systems, lower organisms, and
nonbiological systems for biomedical research. Nonmammalian
model systems can, and do, provide opportunities to advance
the understanding of biological processes and may provide
valuable insights into mechanisms of biological function.
Proposals for the study of appropriate invertebrates, lower
vertebrates, microorganisms, cell and tissue culture
systems, or mathematical and computer approaches should be
regarded as having the same potential importance to
biomedical research as proposals for work on systems that
are phylogenetically more closely related to humans.
Information yielded by such systems can increase
substantially the knowledge of human disease and function.
RESEARCH GOALS AND SCOPE
The overall objective of this RFA is to stimulate research
in the development of nonmammalian models. The following
areas are of particular interest:
o Research on systems that have the potential of becoming
high connectivity models. High connectivity models are
those models where the body of knowledge about the system is
large, and has resulted in extensive cross information, or
connection, with other systems. An organism that has the
potential of becoming a high connectivity model usually has
some information already known about the system. For
example, the metabolism and development of an organism may
be well understood, but other important aspects have not
been explored as fully as possible.
o Research on organisms that are considered high
connectivity models. A few taxa, such as E. coli, S.
cerevisiae, C. elegans, and D. melanogaster, have been
broadly studied from many points of view. Applications that
explore specific areas to close conspicuous gaps in
information about the model will increase the connectivity
of that system.
o Development of model organisms with special features that
have become useful because the data is readily transferable
to humans. An organism may eventually become a better model
or even a high connectivity model if substantial information
on the genetics or functions of that system are known.
o Formulation of mathematical models, in particular when
closely coupled to biological experimentation. There are
opportunities for mathematical modeling in many areas of
biomedical research and at all levels of biological
organization.
MECHANISM OF SUPPORT
The support mechanism for this program will be the
traditional investigator-initiated research grant. Support
for grants is contingent upon receipt of appropriated funds.
It is anticipated that four to six meritorious applications
will be funded. Up to five years of support may be
requested. At the end of the initial project period,
investigator-initiated renewal applications may be submitted
for peer review and competition for support through the
traditional mechanism. Applications responding to this RFA
may be given secondary assignments to institutes with
overlapping interest based on the Division of Research
Grants referral guidelines.
All current policies and requirements that govern the
research grant program of the NIH will apply to grants
awarded under this RFA. Awards under this announcement will
be made to foreign institutions only for research of very
unusual merit, need, and promise, and in accordance with
Public Health Service policy governing such awards.
REVIEW PROCEDURES
Applications in response to this solicitation will be
appropriately peer reviewed first for scientific and
technical merit by initial review groups which will be
convened by the Office of Review, DRR, and second by the
National Advisory Research Resources Council at its
September 1990 meeting. The factors to be considered in the
evaluation of scientific merit of each application will be
similar to those used in the review of traditional project
grant applications and include the novelty, originality and
feasibility of approach; the training, experience, and
research competence of the investigator(s); the adequacy of
the experimental design; the suitability of the facilities;
and the appropriateness of the requested budget to the work
proposed.
METHOD OF APPLYING
Letter of Intent.
Prospective applicants are asked to submit, by February 1,
1990, a short letter of intent that includes a descriptive
title of the proposed research, and the names and
affiliation(s) of proposed key investigators. The letter of
intent does not commit the sender to submit an application,
nor is it a requirement for submission of an application.
This letter should be sent to:
Dr. Louise E. Ramm
Acting Director
Biological Models and Materials Resources Program
Division of Research Resources
National Institutes of Health
Westwood Building, Room 8A07
Bethesda, Maryland 20892
Telephone: (301) 402-0630
Format for Applications.
Submit applications on Form PHS 398 (Rev. 10/88), the
application form for research grants. Application kits are
available at most institutional business offices or may be
obtained from the Office of Grants Inquiries, Room 449,
Westwood Building, Division of Research Grants, NIH,
Bethesda, MD 20892.
Applicants should check the box marked "yes" in item 2 of
the PHS 398 face page, and insert "Development of
Nonmammalian Models", and RFA RR-90-01.
THE RFA LABEL FOUND IN THE PHS 398 KIT MUST BE AFFIXED TO
THE BOTTOM OF THE FACE PAGE OF THE ORIGINAL COMPLETED
APPLICATION FORM, PHS 398, AND DUPLICATED ON ALL COPIES.
FAILURE TO USE THIS LABEL COULD RESULT IN DELAYED PROCESSING
OF YOUR APPLICATION SUCH THAT IT MAY NOT REACH THE REVIEW
COMMITTEE IN TIME FOR REVIEW. THERE WILL BE NO OBLIGATION
TO REVIEW SUCH APPLICATIONS.
The completed original application and five (5) signed
photocopies should be sent or delivered to:
Division of Research Grants
Westwood Building, Room 240
National Institutes of Health
Bethesda, Maryland 20892**
One (1) additional copy should be sent to Dr. Louise E. Ramm
at the address listed below.
TIMETABLE
Letter of Intent February 1, 1990
Application Receipt Date April 4, 1990
Review by the National Advisory September 13-14, 1990
Research Resources Council
Anticipated Award Date September 28, 1990
INQUIRIES
Potential applicants are encouraged to request further
information by telephoning:
Louise E. Ramm, Ph.D.
Acting Director
Biological Models and Materials Resources Program
Division of Research Resources
Westwood Building, Room 8A07
5333 Westbard Avenue
Bethesda, Maryland 20892
Telephone: (301) 496-5507
This program is described in the Catalog of Federal Domestic
Assistance, No. 13.306, Laboratory Animal Sciences and
Primate Research Program. Grants will be awarded 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 intergovernmental review requirements of
Executive Order 12372 or to Health Systems Agency review.
REQUEST FOR COOPERATIVE AGREEMENT APPLICATIONS:
RFA-90-CA-02
PREVENTION CLINICAL TRIALS UTILIZING INTERMEDIATE ENDPOINTS
AND THEIR MODULATION BY CHEMOPREVENTIVE AGENTS
P.T. 34; K.W. 0715035, 0740018, 0710095, 0760003, 0755015
NATIONAL CANCER INSTITUTE
Application Receipt Date: March 15, 1990
I. INTRODUCTION
The Division of Cancer Prevention and Control (DCPC),
National Cancer Institute (NCI), invites applications for
cooperative agreements to support clinical trials
directed toward examining the role of various
chemopreventive agents and/or diet in the prevention of
cancer. This is a follow-up to earlier RFAs that
requested grants, and then later, cooperative agreement
proposals in this area.
The primary objective of this solicitation is to encourage
cancer chemoprevention clinical trials that utilize
biochemical and biological markers to identify populations
at risk and/or to provide intermediate endpoints that may
predict later reduction in cancer incidence rates.
These studies may be developed in phases, including a pilot
phase, which could later proceed to a full-scale
intervention. The main emphasis should be on small,
efficient studies aimed at improving future research designs
of chemoprevention trials, providing further biologic
understanding of the trial results, or providing better,
more quantitative and more efficient endpoints for these
trials. After successful completion of the pilot phase
(i.e. demonstrated modulation of marker endpoints by the
intervention), subsequent studies can include Phase III
clinical trials involving the designated agent, the
utilization of the monitoring test system and a cancer
incidence or mortality endpoint.
Investigators may apply at this time for the pilot phase, or
submit an application for both phases. However, if the
application is for the pilot phase only, it must include a
description of its relevance to a broad clinical application
including the chemopreventive agent, marker test system, and
study population which would be the subject of a full scale,
randomized, cancer risk reduction clinical trial.
Applicants funded under this RFA will be supported through
the cooperative agreement mechanism. An assistance
relationship will exist between NCI and the awardees to
accomplish the purpose of the activity. As more fully
described later in this announcement, the recipients will
have primary responsibility for the development and
performance of the activity. However, there will be
government involvement with regard to: (1) assistance in
securing an Investigational New Drug (IND) approval from the
Food and Drug Administration (FDA); (2) coordination and
assistance in obtaining the chemopreventive agent; (3)
monitoring of safety and toxicity; and (4) quality assurance
of the clinical chemistry aspects of the study. Awards will
not be made until all arrangements for obtaining the IND and
the agent are completed. Final awards will also consider
not only the cost of the clinical trial but also the cost of
the agent and, if necessary, its formulation.
This RFA solicitation represents a single competition with
a specified deadline, March 15 1990, for receipt of
applications. All applications received in response to the
RFA will be reviewed by the same NCI
Initial Review Group.
Applications should be prepared and submitted in accordance
with the aims and requirements described in the following
sections:
II. BACKGROUND INFORMATION
A number of compounds and/or dietary components have been
associated with the inhibition of carcinogenesis in animal
models, in vitro systems, and/or epidemiologic
investigations. Results from these studies suggest that
chemopreventive agents, including dietary components, affect
the later stages of carcinogenesis. The best approach to
address confidently the efficacy and safety, as well as the
applicability and effectiveness, for these agents is through
the conduct of clinical trials.
A variety of parameters have become available and may be
used to identify or evaluate risk modulation in selected
target populations by chemopreventive agents. Examples
include reversal of abnormal cytology, prevention or
reversal of nuclear abberations (micronuclei), ornithine
decarboxylase and/or prostaglandin synthetase inhibition,
DNA ploidy alterations, changes in colonic mucosal
proliferation (histology, tritiated thymidine labelling
indices), decreases in fecal mutagens, and oncogene
suppression tests. Markers of precancerous lesions may also
be useful to define populations that may benefit from
chemoprevention trials; however, more information is
required concerning the ability of such markers to predict
and/or modulate cancer incidence. The development of
sensitive and accurate intermediate endpoints should greatly
enhance the ability to design effective cancer risk
reduction trials.
Chemoprevention clinical trials involve a spectrum of
subjects in various categories of risk. These might include
normal human subjects, subjects at high risk due to prior
exposure to carcinogens, subjects with precancerous lesions,
patients having been treated for a primary cancer now free
of disease, and patients treated for primary cancer with
alkylating agents or radiation who are at high risk for
developing second cancers. Methods for identifying
populations at risk and assessing their risk of
developing cancer are therefore major goals of the
chemoprevention program. These studies are expected to
augment the efficient experimental design of clinical trials
leading to lesser number of subjects required to achieve
adequate statistical power.
Tests for risk identification also are of value
because of the multi-step nature of cancer induction and the
different mechanisms by which chemopreventive agents are
known to inhibit the carcinogenic process. Thus, it is
useful to have tests that measure genotoxic exposure as well
as tests that indicate which subjects are in the later (e.g.
promotional, progressional) phase of the carcinogenic
process. It should be emphasized that protocols that
propose use of assays/methods for risk identification must
also include assays that measure biochemical or biological
intermediate markers of cancer endpoints (in the pilot
phase) or measurement of the intermediate endpoints
themselves (in the later Phase III trials).
III. RESEARCH GOALS AND SCOPE
The purpose of this RFA is to solicit applications from
qualified investigators interested in developing and
implementing cancer prevention clinical trials using
biological markers. These trials, which may be designed in
two phases, will examine the role of chemopreventive agents
alone, diet modification alone, or a combination of these
interventions.
A. STUDIES OF SPECIAL INTEREST
Short-term chemoprevention clinical trials that evaluate the
effect of innovative biomedical monitoring tests in high-
risk populations are sought. These tests might be useful to
determine an intermediate endpoint, serve as a basis to
assess cancer risk status or to assess response to a
chemopreventive agent. The modulation of effects by a
chemopreventive agent on tests that are indicative of
neoplastic progression may be an early indicator of its
efficacy. Examples of such tests might include classical
cytological techniques, suppression of oncogene protein
products, etc. Modulation of a biological marker by a
chemopreventive agent might be highly significant in
relation to ultimate cancer prevention. A series of one or
more tests would be included in the chemoprevention
intervention clinical trial, initially to determine baseline
parameters and later as a followup after administration of
the chemopreventive agent. Biological fluids including
urine, blood, sputum, etc., would have to be obtained from
participants for analysis. Priority would be given for
studies with biological monitoring procedures that do not
overlap or duplicate currently funded projects.
The pilot phase should attempt to detect the clinical
activity of the chemopreventive agent rapidly, efficiently,
and in reasonably accurate fashion with a relatively small
number of subjects or in an in vivo or in vitro assay. The
pilot phase is not expected to give a definite answer to the
ultimate value of the chemopreventive agent, which is the
purpose of a larger Phase III study.
However, upon completion of a pilot study, it should be
possible to make a judgement regarding the effectiveness of
the agent to modulate the marker test system (which will be
correlated with modulation of the cancer endpoint in the
Phase III studies). Additionally, the pilot phase is
expected to give an indication of the nature of any short-
term adverse effects related to the particular dose
schedule, information on patient compliance, ability to
measure the agent in body fluids, and any other factors
related to the subsequent clinical trial. These factors may
provide further clarification on the need for a large, full
scale study.
Intervention populations of interest might include:
individuals at high risk at selected cancer sites,
individuals with precancerous lesions, or individuals
presently free of cancer but at risk for second cancers.
Applications should include a suitable representation of
women and minority populations of individuals such as those
aforementioned. If the applicant cannot comply, a reasonable
explanation should be provided.
B. PREPARATION OF THE PROPOSAL
The general instructions providing for the preparation of
the applications contained in the Grant Application Form PHS
398 (Revised 10/88) are to be used in preparing Cooperative
Agreement applications. Because of the Terms of Award
included as Section V, it is important that applicants
indicate in the Research Plan how they will meet the
requirements stated in the RFA for staff involvement. To
ensure that the cooperative agreement remains the
appropriate instrument, awardees submitting competing
continuation and supplemental applications must describe how
they have met the established terms and conditions.
The following items apply to new as well as to competing
continuing proposals:
1. The study must clearly address Phase I, and optionally
II. Phase I must involve the application of a biological
and/or biochemical marker and its modulation by the study
agent. Phase II involves the implementation of a full-scale
randomized, double-blind, risk-reduction, prevention
clinical trial. For applicants seeking to conduct only
Phase I, the study must describe relevance to a clinical
trial application including a marker, agent and target group
that might be appropriate for a full-scale intervention
after completion of the pilot study.
2. The applicant should provide a rationale for selection
of the biological or biochemical marker, its relevance to
risk identification or modulation, and its relevance to the
intervention agent and the target population.
3. The applicant should provide the rationale for selection
of the proposed intervention agent. This should include
relevant epidemiologic and laboratory data. Preclinical and
clinical data on any potential untoward effects of the
intervention agent should also be presented. In
circumstances where there might be some doubt as to the
availability or the safety of the agent, the applicant may
wish to consult with the pharmaceutical company and the NCI
Program Director prior to preparing the application. The
applicant should thus present a reasonable case for the
"readiness" of the proposed intervention agent for a
clinical trial.
4. The applicant should provide a rationale for selection
of a specific target group and provide an estimate of the
number of participants required for the completion of the
study. Criteria and calculations used to estimate sample
size should be included. The applicant should provide a
description of the target population or group chosen and
should justify the selection of this group. The group
should be defined, as appropriate, by age, sex, race,
dietary customs, education, geographic location,
occupational or life style risk factors, and relevancy to a
specific cancer problem or to its possible prevention by the
designated inhibitor(s). The accrual rate should be
estimated. If multiple institutions are involved, the
proposal should include verification of the co-investigators'
willingness to participate, and pertinent additional
information regarding the cooperating institutions' staff
qualifications, resources, research plans, including patient
availability and data flow, as well as corresponding budget
requirements.
5. The applicant should clearly indicate the clinical
chemistry and biologic aspects of the study to include
collection, storage, handling, analysis, and quality control
of biological or biochemical samples. The methods and
equipment to be used and the technical qualifications and
experience of the personnel involved must be addressed. If
these aspects of the study are to be conducted by groups
other than at the applicant's institution, a letter from the
cooperating institutions indicating their willingness to
participate should be included.
6. The applicant should elucidate any known or potential
safety or toxicity considerations, the techniques and
procedures to monitor and report any adverse health effects
and appropriate dose modifications based on toxicity
monitoring.
7. The applicant should specify the methods to be used to
document nutrient intake, if indicated, and adherence to the
prescribed intervention during the course of the trial.
8. The applicant must indicate a willingness to work
cooperatively with the assistance of the Program Director
in the implementation and conduct of the study.
IV. MECHANISM OF SUPPORT
This RFA will use the cooperative agreement mechanism. The
cooperative agreement is an assistance mechanism in which
limited NIH programmatic involvement with the recipient
during performance of the planned activity is anticipated.
The nature of Program Director's involvement is described in
Section V. Responsibility for the planning, direction, and
execution of the proposed project will be solely that of the
applicant/awardee. Except as otherwise stated in this RFA,
awards will be administered under PHS grants policy as
stated in the Public Health Service Grants Policy Statement,
DHHS Publication No. (OASH) 82-50,000, revised January 1,
1987.
This RFA will be issued annually for three years. However,
should the NCI determine that there is a sufficient
continuing program need, NCI may invite all funded
recipients to submit competing continuation applications.
Approximately $1 million in total costs per year for 3 to 5
years will be committed to fund applications
that are submitted in response to this RFA. It is
anticipated that 3 to 5 awards will be made annually. This
funding level is dependent on the receipt of a sufficient
number of applications of high scientific merit. The total
project period for applications submitted in response to the
present RFA should not exceed 5 years. The earliest
feasible start date for the initial awards will be December
1, 1990. Although this program is provided for in the
financial plans of the NCI,
awards made pursuant to this RFA will be contingent upon the
continued availability of funds for this purpose.
Non-profit and for-profit institutions are eligible to
apply. Foreign as well as domestic institutions are
eligible.
V. TERMS OF AWARD
These special terms of award are in addition to, and not in
lieu of, otherwise applicable OMB administrative guidelines,
HHS grant regulations 45 CFR 74 and other Health and Human
Services, Public Health Service and NIH grants
administration policy.
The NCI will provide appropriate assistance, advice and
guidance as described below. The role of the NCI will be to
facilitate, not to direct.
A. PROGRAM STAFF INVOLVEMENT
1. STUDY/PROTOCOL PLAN
The NCI Program Director may assist the awardee in the study
and protocol design by providing information regarding: a)
the nature of concurrent studies in the area of research,
pointing out possible duplication of effort, b) safety and
toxicity of proposed regimens, and c) availability of
necessary drugs. The NCI Program Director may also offer
advice regarding the scientific rationale, priority, design
and implementation of the proposed studies. A safety
and protocol review will be undertaken on all clinical
trials from proposals that are ultimately funded. Such
a review is legally required by the Food and Drug
Administration to assure that all safety, toxicity,
monitoring and reporting issues are in conformance with
Investigational New Drug guidelines. The awardee
institution and principal investigator must agree to comply
with the recommendations of the review.
2. DATA ACCESS
The Program Director will have access to the data to review
toxicity and safety aspects of the project, prepare IND
applications and monitor any trial aspects required by other
federal agencies. This information is necessary to satisfy
FDA regulations with regard to CFR 21. Data generated,
however, are the property of the awardee institution. The
Program Director may encourage and facilitate sharing of
data between investigators when this is in the mutual
interest of the investigators and the NCI.
3. INVESTIGATIONAL NEW DRUG
The NCI will have the option to cross file or independently
file an IND on investigational drugs evaluated in trials
supported under the cooperative agreements.
The NCI will advise investigators of specific requirements
and changes in requirements concerning investigational drug
management for compliance with NCI and the FDA guidelines
and regulations. Investigators conducting trials under
cooperative agreements will be expected, in cooperation with
the NCI, to comply with all FDA monitoring and reporting
requirements for investigational agents, for reporting
adverse reactions, and for maintaining necessary records of
drug receipt and distribution.
4. ASSISTANCE WITH OBTAINING OR PURCHASING INVESTIGATIONAL
DRUGS
The NCI may assist the investigator to obtain the agent to
be used in the proposed study. Once the application is
approved by the peer review committee, the NCI, and the
National Cancer Advisory Board, the NCI Program Director may
begin discussions with the principal investigator and
pharmaceutical industry with regard to obtaining the drug.
In the event a suitable agent is not available at no cost,
the NCI may proceed to purchase the agent through normal
procurement mechanisms. Purchase of the agents is only
undertaken after measures to obtain the drug at no cost have
been exhausted. Awards will not be made until all
arrangements for obtaining the agent are complete. Final
awards by the NCI will also consider not only the cost of
the trial but also the cost of the agent, including its
formulation, encapsulation and packaging, if these costs are
to be borne by the Government.
5. PROTOCOL DISAPPROVAL
Protocols may be disapproved by the NCI on the basis of
patient safety and toxicity, failure to meet FDA regulations
concerning NCI-sponsored investigational drugs, obvious
duplications or failure to satisfy the goals of the RFA or
of the awardee applications. The Arbitration Mechanism is
described in Section V-8 below.
6. PROTOCOL MODIFICATION
No protocol modifications shall be implemented without
approval from the Program Director, and also from the FDA,
if indicated.
7. PROTOCOL TERMINATION
The Program Director may request that a protocol study be
terminated. Reasons for this request may be a) insufficient
accrual, b) further accrual will not add information of
scientific value, and/or c) consideration of patient safety.
The NCI will not provide drugs or IND sponsorship for a
study after requesting termination. Investigators who wish
to challenge protocol termination may do so according to the
arbitration process described below. If the request to
terminate a study is upheld by the arbitration panel, but
the awardee chooses to continue the study, the results of
that study will be subject to careful monitoring through
progress reports. In addition, the NCI may withdraw funding
for such a protocol if the grounds for termination are
patient safety and toxicity. The Arbitration Mechanism is
described in Section V-8.
8. DESCRIPTION OF ARBITRATION MECHANISM
When mutually acceptable agreements on the safety of
research protocols, protocol disapproval or protocol
termination cannot be obtained between investigators and the
NCI staff committee, as described above, an arbitration
panel composed of one member of the grant recipient group,
one NCI nominee, and a third member with appropriate
expertise chosen by the other two members will be formed to
review NCI decisions. 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.
9. CLINICAL TRIALS PROGRESS REVIEW
Progress will be evaluated semi-annually by the Program
Director from material presented in the awardee's
semi-annual report (as described in Section V.B.4.A. below).
Recommendations of the Program Director will be communicated
by letter to the investigator to which he/she is expected to
respond.
Insufficient numbers of patients accrued to attain the
stated delta value (d=difference between treatments to
be detected divided by standard deviation), unsatisfactory
progress, or non-compliance with terms of award may result
in a reduction of the budget, withholding of support,
suspension or termination of the award.
10. QUALITY ASSURANCE
a. The NCI has established a clinical chemistry quality
assurance program with the National Institute of Science and Technology,
Gaithersburg, Maryland, which will provide chemical standards
for some of the agents that will be used and assayed for in
the clinical trials. These standards will contribute to the
quality control of selected laboratory determinations. The
awardee will participate in the laboratory quality control
activity when so notified.
b. Periodically, the NCI staff will review the mechanisms
established by each awardee for quality control of clinical
studies. These mechanisms must conform with
FDA regulations.
11. OTHER TERMS
No patients may be enrolled in this study without the prior
written approval of the program director for this
cooperative agreement including submission to and approval
by the FDA of an IND application and satisfactory response
to the recommendations of the safety and protocol review.
B. RESPONSIBILITIES OF AWARDEES
1. SAFETY AND TOXICITY REVIEW
The awardee institution and principal investigator agree to
comply with the recommendations of the safety and protocol
review.
2. QUALITY CONTROL AND ADVERSE REACTION REPORTING
a. The awardee is required to set up mechanisms for quality
control. Some or all of the following may be relevant:
compliance with protocol requirements for eligibility;
treatment and follow-up; laboratory data; dietary data;
pathological materials; and operative reports.
b. The awardee agrees to perform the study according to the
approved protocol and consent forms. Any proposed changes
in the protocol must receive the advance permission of the
NCI Program Official for this award.
c. The awardee is required to conform to NCI guidelines for
the use of investigational drugs including investigator
registration (FDA Form 1573), maintaining a record of drug
receipt and reporting of adverse drug reactions. Life
threatening or unexpected toxicity MUST by reported by the
investigator IMMEDIATELY by telephone to the NCI Program
Official shown on the Notice of Award and confirmed with
details in writing within two weeks. The investigator will
be responsible for amending protocols and consent forms
based on new toxicity information sent to the investigators
by NCI staff.
3. INFORMED CONSENT; IRB APPROVAL
a. Approval by the Institutional Review Board (IRB) must be
obtained by awardees on all protocols because of the
involvement of human subjects.
b. Informed Consent Forms must comply with HHS Regulations
and NIH guidelines and should include preclinical and
clinical toxicology information as relevant. Changes in
the Consent Forms submitted by the awardee should be
reported to the NCI.
c. Awardees will be responsible for amending Informed
Consent forms if new toxicity information becomes available.
4. DATA MANAGEMENT AND REPORTING REQUIREMENTS
Data acquisition and analysis is the responsibility of the
investigator. Data that must be collected are listed in
the protocol format available from the Program Director.
Investigators will be required to submit reports to NCI
using the following schedule and format:
A. Semi-annual Reports
Semi-annual scientific reports should report on the progress
of the project during the previous six months and the
cumulative progress of the study.
The Semi-annual Report should include:
1. A concise narrative progress summary covering the
previous six months (give dates of the six-month period
covered) and the cumulative progress of the study.
2. Tabular display of:
a. Accrual history of the project presented in six-month
periods. In addition to total accrual, the investigator
should report the number recruited but ineligible, number
inevaluable, and number of study violations.
b. Interim analyses of results, if appropriate.
c. Toxicities, graded as to severity.
3. Explanation in case of any of the following: increase
or decrease in accrual, any unusual or unexpected incidence
of ineligible or inevaluable participants, or any unusual or
unexpected study violations.
4. Brief description of quality control measures such as
review of records, on-site monitoring, biochemical
monitoring of study compliance, etc.
5. A list of all publications related to work under this
cooperative agreement. This listing should include
published references, manuscripts in press or submitted.
Submit two copies of each reprint.
6. Curriculum vitae should be provided if there has been a
change in any of the project investigators.
B. Final Study Report
The final report of a completed study shall consist of
detailed analyses of results and toxicity, plans for
publications, a comprehensive list of all previous
publications related to the project, and plans for archiving
and storing the study records.
VI. REVIEW PROCEDURES AND CRITERIA
A. REVIEW PROCEDURE
Upon receipt, applications will be reviewed (initially) by
DRG for completeness. Incomplete applications will be
returned to the applicant without further consideration.
Evaluation for responsiveness to the RFA is an NCI program
staff function. Applications will be judged to determine if
they meet the goals and objectives of the program as
described in the RFA. Applications that are judged
non-responsive will be returned but may be submitted as
investigator-initiated grants at the next receipt date.
Questions concerning the relevance of proposed research to
the RFA should be directed to the Program Director
identified in Section VIII.
If the number of applications is large compared
to the number of awards to be made, the NIH may conduct a
preliminary scientific peer review to eliminate those which
are clearly not competitive. The NIH will administratively
withdraw from competition those applications judged to be
noncompetitive and notify the applicant and institutional
business official.
Those applications judged to be both competitive and
responsive will be further evaluated, using the review
criteria shown below, for scientific and technical merit by
an appropriate peer review group convened by the Division of
Extramural Activities, NCI. The second level of review by
the National Cancer Advisory Board considers the special
needs of the Institute and the priorities of the National
Cancer Program.
B. REVIEW CRITERIA
In order to be responsive to this RFA, applications must
be directed towards the attainment of the stated
programmatic goals and fall within one or more of the
specified research categories (see RESEARCH GOALS AND
SCOPE). If an application is judged by the Program
Director to be non-responsive, the applicant will have the
opportunity to resubmit the application for review by the
appropriate NIH review group along with other unsolicited
applications received by the NIH in the grant application
review cycle which is current at that time.
The following factors will be considered in evaluating the
scientific merit of each response to the RFA:
1. Extent of relevance to the overall goals and objectives
of the RFA.
2. Scientific merit of the study objective(s), design, and
methodology to include considerations of toxicity, safety
and quality assurance.
3. Basic and clinical scientific significance as well as
originality of the proposed research.
4. Research experience and/or competence of the Principal
Investigator and other key personnel to conduct the proposed
studies.
5. Adequacy of time (effort) which the Principal
Investigator and staff would devote to conduct the proposed
studies.
6. Relevancy and appropriateness of the specific target
population along with assurance as to its accessibility.
7. Identity of sources of data, tissues, fluids, etc.,
procedures for their collection and analysis, and assurances
as to their accessibility.
8. Availability of the chemopreventive agents or dietary
factors. If an IND is held for the agent, that information
should be furnished at the time of proposal submission. If
the NCI is to assist in obtaining the IND, that information
should be furnished.
9. Adequacy of plans for NCI program staff involvement with
the proposed studies.
The review group will examine critically the submitted
budget and will recommend an appropriate budget and period
of support for each approved application.
VII. METHOD OF APPLYING
The regular research grant application form PHS-398 (revised
10/88) must be used in applying for these grants. These
forms are available at most institutional business offices;
from the Office of Grants Inquiries, Division of Research
Grants, National Institutes of Health, Room 449, Westwood
Building, 5333 Westbard Avenue, Bethesda, Maryland 20892; or
from the NCI Program Director named below.
The RFA label available in the revision of Application Form
398 must be affixed to the bottom of the face page. Failure
to use this label could result in delayed processing of your
application such that it may not reach the review committee
in time for review. In addition, the title of the
application, "Prevention Clinical Trials Utilizing
Intermediate Endpoints and Their Modulation by
Chemopreventive Agents", and the RFA number, 90-CA-02,
should be typed in block 2 of the face page of the
application form.
Submit a signed, typewritten original of the application,
including the Checklist and four (4) signed, exact
photocopies, in one package to the Division of Research
Grants at the address below. The photocopies must be clear
and single sided.
DIVISION OF RESEARCH GRANTS
National Institutes of Health
Westwood Building, Room 240
Bethesda, Maryland 20892**
At time of submission, two (2) additional copies of the
application should be sent to:
REFERRAL OFFICER
Division of Extramural Activities
National Cancer Institute
Room 848, Westwood Building
5333 Westbard Avenue
Bethesda, Maryland 20892
Applications must be received by March 15, 1990. If an
application is received after that date, it will not be
accepted and will be returned. Also, the Division of
Research Grants (DRG) will not accept any application in
response to this announcement that is the same as one
currently being considered by any NIH awarding unit.
VIII. LETTER OF INTENT
Prospective applicants are asked to submit, by February 9,
1990, a letter of intent that includes a descriptive title
of the proposed research, the name and address of the
principal investigator, the names of other key personnel,
the participating institutions, and the number and title of
the RFA in response to which the application is being
submitted.
Although a letter of intent is not required, is not binding,
and does not enter into the review of subsequent
applications, the NCI would like to emphasize the benefits
to the applicant of having a principal investigator submit a
letter of intent.
The letter of intent should be sent to:
Marjorie Perloff, M.D.
Chemoprevention Branch
Executive Plaza North, Suite 201
National Institutes of Health
9000 Rockville Pike
Bethesda, Maryland 20892-4200
Telephone: (301) 496-8563
IX. INQUIRIES
Written or telephone inquiries concerning the objectives and
scope of this RFA or inquiries about whether or not specific
proposed research would be responsive are encouraged and
should be directed to the Program Director, Marjorie
Perloff, M.D. at the above address. She welcomes the
opportunity to clarify any issues or questions from
potential applicants.
This program is described in the Catalog of Federal Domestic
Assistance Number 13.399, Cancer Control. Awards will be
made under the authority of the Public Health Service Act,
Title IV, Section 301 (Public Law 78-410,; 42 U.S.C. 241,
and Section 412, as amended by Public Law 99-158, 42 U.S.C.
258a-1); and administered under PHS grant policies and
Federal regulations 42 CFR Part 52 and 45 CRF Part 74. This
program is not subject to the intergovernmental review
requirements of Executive Order 12372 or Health Systems
Agency review.