kristoff@GENBANK.BIO.NET (Dave Kristofferson) (01/13/90)
Vol. 19, No. 2, January 12, 1990
DATED ANNOUNCEMENTS (RFPs AND RFAs)
AIDS COMMUNITY-BASED OUTREACH/INTERVENTION RESEARCH PROGRAM
(RFA DA-90-02) ......................................(84/205)................ 1
National Institute on Drug Abuse
Index: DRUG ABUSE
VIRAL ONCOGENESIS AND PATHOGENESIS OF HEPATOCELLULAR CARCINOMA
(RFA 90-CA-08) ......................................(208/343, 644/975)...... 2
National Cancer Institute
Index: CANCER
ONGOING PROGRAM ANNOUNCEMENTS
MOLECULAR APPROACHES TO DRUG ABUSE RESEARCH .........(349/514)............... 4
National Institute on Drug Abuse
Index: DRUG ABUSE
ERRATA
NCI/MARC SUMMER TRAINING SUPPLEMENT (PA) ............(520/537)............... 6
National Cancer Institute
Index: CANCER
INVESTIGATIONS INTO METHODS THAT REPLACE OR REDUCE VERTEBRATE ANIMALS
USED IN RESEARCH, OR LESSEN THEIR PAIN AND DISTRESS (PA) ..(540/568)......... 6
National Institutes of Health
Alcohol, Drug Abuse, and Mental Health Administration
Index: NATIONAL INSTITUTES OF HEALTH
ALCOHOL, DRUG ABUSE, AND MENTAL HEALTH ADMINISTRATION
DATED ANNOUNCEMENTS (RFPs AND RFAs)
AIDS COMMUNITY-BASED OUTREACH/INTERVENTION RESEARCH PROGRAM
RFA AVAILABLE: DA-90-02
P.T. 34, FF; K.W. 0715008, 0403004, 0404021, 0411005
National Institute on Drug Abuse
APPLICATION RECEIPT DATE(S)
Receipt Initial Advisory Council Earliest
Date Review Date Start Date
March 12* June/July Sept/Oct November
* After this special receipt date, applications may be submitted to this
announcement using the regular AIDS receipt dates.
PURPOSE
The purpose of this research grant program is to announce a cooperative
agreement program to evaluate the efficacy of community-based intervention
strategies designed to prevent and reduce the spread of AIDS among intravenous
(IV) drug users, their sexual partners, and those at demonstrable risk for
intravenous drug use.
RESEARCH OBJECTIVES
Emphasis is placed on gaining an understanding of the efficacy of different
innovative strategies for containing the spread of AIDS within and from
high-risk populations, e.g., IV drug users who are not in treatment, their
sexual partners, and those at demonstratable risk for intravenous drug use.
There is also a large concern with monitoring and understanding the nature of
risk-taking behavior within communities and groups over time. Consequently,
the National Institute on Drug Abuse (NIDA) will continue to facilitate
grantee collaboration and will make a closed-ended interview schedule, the
AIDS Initial Assessment, to be administered to all subjects admitted into the
applicant's study. This instrument is to be administered as a baseline
measure prior to HIV testing and/or the initiation of traditional or
innovative interventions. The applicant will also state hypotheses s/he will
be testing in the course of the study. It is expected that outcome variables
will consist of at least the following: (a) reduction in risk-taking
behaviors associated with needle use and with sexual behaviors; (b) increases
in knowledge about AIDS transmission and risk factors. Beyond the outcome
study and the description/monitoring of risk-taking behaviors and knowledge
regarding AIDS transmission, the applicant should plan for the conduct of
sub-studies relevant to an understanding of the issues involved in planning
and developing AIDS prevention programs for the different populations they are
studying.
INCLUSION OF MINORITIES IN STUDY POPULATIONS
The Alcohol, Drug Abuse, and Mental Health Administration (ADAMHA) urges
applicants to give added attention (where feasible and appropriate) to the
inclusion of minorities in study populations for research into the etiology of
diseases, research in behavioral and social sciences, clinical studies of
treatment and treatment outcomes, research on the dynamics of health care and
its impact on disease, and appropriate interventions for disease prevention
and health promotion. If minorities are not included in a given study, a
clear rationale for their exclusion should be provided.
INCLUSION OF WOMEN IN STUDY POPULATIONS
ADAMHA urges applicants to consider the inclusion of women in the study
populations for all clinical research efforts. Exceptions would be studies of
diseases which exclusively affect males or where involvement of pregnant women
may expose the fetus to undue risks. Gender differences should be noted and
evaluated. If women are not to be included, a clear rationale should be
provided for their exclusion.
In order to provide more precise information to the treatment community, it is
recommended that publications resulting from ADAMHA-supported research in
which the study population was limited to one sex for any reason other than
that the disease or condition studied exclusively affects that sex, should
Vol. 19, No. 2, January 12, 1990 - Page 1
state, in the abstract summary, the gender of the population studied, e.g.,
"male patients," "male volunteers," "female patients," "female volunteers."
AVAILABILITY OF FUNDS
It is estimated that in FY 1990, up to 20 projects may be funded under this
announcement. Applications received in response to this announcement will
compete for approximately $7 million in FY 1990 grant money expected to be
available for this purpose.
REVIEW PROCEDURES
Applications received under this announcement will be assigned to an initial
reveiw group for scientific and technical merit review. Such groups consist
primarily of non-Federal experts. Notification of review outcome will be sent
to the applicant as soon as it is available. Applications will receive a
secondary review by the National Advisory Council of the National Institute on
Drug Abuse whose review may be based on policy considerations as well as
scientific merit. Only applicants recommended for approval by the National
Advisory Council will be considered for funding.
APPLICATION PROCEDURES
Applicants must use the standard PHS-398 (Rev. 10/88) research grant
application form. "AIDS Community-based Research Program" should be typed on
Item #2 on the face page of the PHS 398 form and check the YES box.
Application kits containing the necessary forms and instructions may be
obtained from the following office:
Grants Management Branch
National Institute on Drug Abuse
5600 Fishers Lane, Room 8-A-54
Rockville, Maryland 20857
Telephone: (301) 443-6710
INQUIRIES
Further information and consultation on program requirements can be obtained
from:
Chief, Community Research Branch
National Institute on Drug Abuse
5600 Fishers Lane, Room 9-A-30
Rockville, Maryland 20857
Telephone: (301) 443-6720
VIRAL ONCOGENESIS AND PATHOGENESIS OF HEPATOCELLULAR CARCINOMA
RFA AVAILABLE: 90-CA-08
P.T. 34; K.W. 0715035, 0705025, 0765033, 1002045
National Cancer Institute
Letter of Intent Receipt Date: June 4, 1990
Application Receipt Date: August 3, 1990
INTRODUCTION
A diverse group of viral agents are etiologically associated with human viral
hepatitis, some of which are also associated with chronic sequelae that may
progress to primary hepatocellular carcinoma (PHC). Hepatitis B virus (HBV)
is a double-stranded DNA virus that occurs worldwide and can be transmitted by
contaminated blood, blood products, or unsterile needles. In addition,
horizontal spread of the virus occurs, particularly among young children, by
contamination of mucous membranes or small breaks in the skin with
contaminated secretions from infected playmates. Perinatal (vertical)
transmission from HBV-infected mothers to offspring also occurs and is a
particularly important mode of transmission in Asia. HBV progresses to a
chronic infection or chronic carrier state in 5-10 percent of the adult
clinical cases and has been strongly associated with the etiology of PHC.
The term "non-A, non-B hepatitis virus" (NANBH) describes viral hepatitis that
occurs in the absence of serologic markers for known hepatotropic agents such
as hepatitis A virus (HAV), HBV, or other viruses such as cytomegalovirus or
Epstein-Barr virus that are associated with hepatitis-like symptoms. Three
epidemiologic forms of human NANBH, called "blood-transmitted",
Vol. 19, No. 2, January 12, 1990 - Page 2
"coagulation-factor-transmitted", and "enteric" or "waterborne", have been
proposed based on studies in primate models. NANBH agents cause an acute
hepatitis that is somewhat milder than HBV induced disease; however, it has
been estimated that at least half of the NANBH infections result in chronic
hepatitis, which in turn results in cirrhosis in approximately 20 percent of
these cases. Chronicity and cirrhosis carry increased risk of PHC. NANBH is
of particular significance in the U.S. since up to 10 percent of transfusions
in the U.S. are thought to result in hepatitis and more than 90 percent of the
transfusion-associated hepatitis in the U.S. is associated with NANB agents.
The "blood transmitted" form of NANBH, also referred to by some investigators
as hepatitis C virus (HCV), has an RNA genome and is the only one of these
agents currently associated with primary hepatocellular carcinoma.
This Request for Applications (RFA) is for a single competition with a
deadline of August 3, 1990, for receipt of applications, and June 4, 1990, for
receipt of letters of intent. Applications should be prepared and submitted
in accordance with the aims and requirements described in the complete RFA
document which may be obtained from the program director listed in the
INQUIRIES section.
RESEARCH GOALS AND SCOPE
The overall thrust of this RFA is to stimulate research on the human hepatitis
viruses associated with liver cancer (e.g. HBV, NANBH or HCV), and their
interactions with environmental factors (e.g., dietary aflatoxin), and host
factors (chromosomal fragility, immune response) in order to identify the
mechanism(s) involved in establishment of chronicity, cell transformation, and
PHC. Examples of research objectives would include the following: (i)
development and/or use of sensitive and specific assays for blood-borne NANBH
(HCV) to determine the possible role of this agent in PHC; (ii) determination
of the prevalence of HBV strains resistant to currently available vaccines and
the role of genetic variation of HBV isolates in this process; (iii)
definition of the role of the HBV X gene in transformation; (iv) systematic
studies of co-carcinogenesis (viral, chemical, and/or dietary factors) in the
development of PHC in animal models of human cancer (e.g. the woodchuck); (v)
determination, in transgenic animals, of the oncogenic potential of specific
viral gene products; (vi) determination of the possible role of cellular
oncogenes or anti-oncogenes in PHC; (vii) investigation of the role of
chromosomal abnormalities in susceptibility to PHC; and (viii) measurement of
the host response to individual viral proteins with the goal of delineating
the host response to different viral antigens in hepatitis-associated
pre-malignant and malignant sequelae.
Where appropriate, collaborative arrangements to facilitate the achievement of
research goals should be considered.
Applications should contain as goals both methodological development and
application to a specific area of HBV or HCV oncogenesis as well as studies of
possible synergistic interactions between viruses, alcohol, aflatoxins, etc.;
basic and/or clinical issues are considered as appropriate subjects for this
RFA.
MECHANISM OF SUPPORT
This RFA will use the National Institutes of Health (NIH) grant-in-aid (RO1).
Responsibility for the planning, direction and execution of the proposed
project will be solely that of the applicant. Except as stated in this RFA,
awards will be administered under PHS grants policy as described in the Public
Health Service Grants Policy Statement, DHHS Publication No. (OASH) 82-50,000,
revised January 1, 1987.
This RFA is a one-time solicitation. Generally, future unsolicited competing
renewal applications will compete as research project applications with all
other investigator-initiated applications and be reviewed in a standing
Division of Research Grants study section. However, should the National
Cancer Institute (NCI) determine that there is a sufficient continuing program
need, NCI may announce a request for renewal applications.
Approximately $1,000,000 in total costs per year for five (5) years will be
committed to fund applications that are submitted in response to this RFA.
Actual funding 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 five
(5) years. The earliest feasible start date for the initial awards will be
April 1, 1991. Although this program is provided for in the financial plans
of the NCI, award of grants pursuant to this RFA is also contingent upon the
availability of funds for this purpose. Non-profit and for-profit
Vol. 19, No. 2, January 12, 1990 - Page 3
institutions are eligible to apply, as are both foreign and domestic
institutions.
INQUIRIES
A copy of the complete RFA describing the research goals and scope, the review
criteria, and the method of applying can be obtained by contacting:
Dr. John S. Cole, III
Program Director
RNA Virus Studies II
Biological Carcinogenesis Branch
Division of Cancer Etiology
National Cancer Institute
Executive Plaza North, Room 540
Bethesda, Maryland 20892
Telephone: (301) 496-1718
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 Dr. Cole at the above
address. The program director welcomes the opportunity to clarify any issues
or questions from potential applicants.
ONGOING PROGRAM ANNOUNCEMENTS
MOLECULAR APPROACHES TO DRUG ABUSE RESEARCH
P.T. 34; K.W. 0404009, 1002008, 0760075, 0765010
National Institute on Drug Abuse
PURPOSE
The purpose of this announcement is to stimulate basic research in the
molecular biology of the addictive process. In general, research is needed
to: (1) identify and elucidate the structure of cellular membrane components
such as receptors and transporters with specific affinity for drugs of abuse;
(2) establish the biosynthetic pathways by which inter- and intra-cellular
messengers involved in the addictive process are synthesized, modified and
degraded; (3) explore the molecular mechanism(s) involved in tolerance,
dependence, craving and other manifestations of the addictive process; and (4)
develop new methods and resources to facilitate the study of the addictive
process at the molecular level.
RESEARCH OBJECTIVES*
The National Institute on Drug Abuse (NIDA) encourages the submission of
research proposals to gather and integrate information at the molecular
biology and genetic levels in order to understand the underlying basis of
addiction, the consequences of long-term drug abuse, and to generate better
strategies for effective diagnosis, treatment, education and prevention.
Examples of particular interest include the following:
1. Neuropeptides: Studies of the expression, processing and distribution of
various relevant neuropeptide genes at different developmental stages.
2. Receptors: Efforts to study the cloned genes of receptors, ion channels
and transporters in terms of genomic organization, chromosomal localization as
well as the regulation of their expression.
3. Genetic Factors of the Addiction Processes: Development of strains of
animals exhibiting variation in drug preference, vulnerability, tolerance and
dependence to abused substances, studies to uncover the genes responsible for
these variations.
MECHANISM OF SUPPORT
Support can be obtained in the form of RO1 (Research Project Grants), RO3
(Small Grants), R13 (Research Conference Grants), R29 (First Independent
Research Support and Transition Awards).
Vol. 19, No. 2, January 12, 1990 - Page 4
ELIGIBILITY
Application for research grants may be submitted by any public or private
non-profit or for-profit institution such as universities, colleges,
hospitals, laboratories, units of State or local government, private industry
and eligible agencies of the Federal Government. Women and minority
investigators are encouraged to apply.
APPLICATION PROCEDURES
Applicants should use the grant application form PHS-398 (Rev. 10/88). The
title of this Program Announcement, "Molecular Approaches to Drug Abuse
Research," should be typed in item number 2 on the face page of the PHS-398
application form.
Application kits containing the necessary forms and instructions may be
obtained from business offices or offices of sponsored research at most
colleges, universities, medical schools, and other major research facilities.
If such a source is not available, the following office may be contacted for
the necessary application material:
Grants Management Branch
National Institute on Drug Abuse
5600 Fishers Lane, Room 10-25
Rockville, Maryland 20857
Telephone: (301) 443-6710
The signed original and six (6) permanent, legible copies of the completed
application should be sent to:
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, Maryland 20892**
RECEIPT AND REVIEW SCHEDULE
The schedule for receipt and review is as follows:
Receipt Initial Advisory Council Earliest
Dates Review Review Start Date
(New/Renewal)
Jun 1/Jul 1# Oct/Nov Jan/Feb Apr 1
Oct 1/Nov 1# Feb/Mar May/June July 1
Feb 1/Mar 1# May/June Sep/Oct Dec 1
# Amended applications (new or renewal) are to be submitted on these dates.
Applications received after the above receipt dates are subject to assignment
to the next review cycle or may be returned to the applicant.
REVIEW PROCESS
The Division of Research Grants, NIH, serves as a central point for receipt of
applications for most discretionary PHS grant programs. Applications received
under this announcement will be assigned to an Initial Review Group (IRG) in
accordance with established PHS Referral Guidelines. The IRGs, consisting
primarily of non-Federal scientific and technical experts, will review the
applications for scientific and technical merit. Notification of the review
recommendations will be sent to the applicant after the initial review.
Applications will receive a second-level review by an appropriate National
Advisory Council whose review may be based on policy considerations as well as
scientific merit. Only applications recommended for approval by the Council
may be considered for funding.
Applications submitted in response to this announcement are not subject to the
intergovernmental review requirements of Executive Order 12372, as implemented
through Department of Health and Human Services regulations at 45 CFR Part 100
and are not subject to Health Systems Agency Review.
REVIEW CRITERIA
Criteria for scientific/technical merit review of applications will include
the following: significance and originality from a scientific or technical
standpoint of the goals of the proposed research; adequacy of the methodology
proposed to carry out the research; feasibility of the principal investigator
and other key research personnel; availability of adequate facilities, other
Vol. 19, No. 2, January 12, 1990 - Page 5
resources, and collaborative arrangements necessary for the research;
appropriateness of budget estimates for the proposed research activities; and
adequacy of provision for the protection of human subjects and the welfare of
animal subjects, as applicable.
AWARD CRITERIA
Applications recommended for approval by the National Advisory Council on Drug
Abuse will be considered for funding on the basis of overall scientific and
technical merit of the research as determined by peer review, National
Institute on Drug Abuse needs and balance, and availability of funds.
INQUIRIES
The guidelines, other information about the drug abuse research grants
program, and further information about areas of interest described in this
announcement may be obtained by contacting:
Dr. Theresa Lee
Biomedical Branch
National Institute on Drug Abuse
5600 Fishers Lane, Room 10A-31
Rockville, Maryland 20857
Telephone: (301) 443-6300
* Other components of the Alcohol, Drug Abuse, and Mental Health
Administration (ADAMHA) share an interest in several of the research areas
described in this announcement. Projects may be submitted under this
announcement that address issues in common with the National Institute on
Alcohol Abuse and Alcoholism. Joint funding of such projects is possible;
however, preapplication consultation is strongly encouraged. Applications are
considered for acceptance and assigned according to standing Institute
referral guidelines. Referencing this announcement does not guarantee
assignment to NIDA.
ERRATA
NCI/MARC SUMMER TRAINING SUPPLEMENT
P.T. 42, FF; K.W. 0720005, 0715035, 1014006
National Cancer Institute
Application Receipt Date: February 1, 1990
In the above captioned Program Announcement published in the December 1, 1989
issue of the NIH Guide for Grants and Contracts (Vol. 18, No. 43), a portion
of the first paragraph was omitted. The correct version appears below:
The Comprehensive Minority Biomedical Program (CMBP) of the Division of
Extramural Activities (DEA), National Cancer Institute (NCI), invites
interested grantee institutions that have Minority Access to Research Careers
(MARC) grants to apply for CMBP support of MARC scholars interested in
obtaining laboratory research experience at the NCI. This program
announcement will be issued on an annual basis.
INVESTIGATIONS INTO METHODS THAT REPLACE OR REDUCE VERTEBRATE ANIMALS USED IN
RESEARCH, OR LESSEN THEIR PAIN AND DISTRESS
P.T. 34; K.W. 0755020, 0780010, 0780015, 0780020
National Institutes of Health
Alcohol, Drug Abuse, and Mental Health Administration
The following is a correction in the NIH-wide Program Announcement entitled,
"Investigations Into Methods That Replace Or Reduce Vertebrate Animals Used In
Research, Or Lessen Their Pain And Distress" published in the NIH Guide for
Grants and Contracts, Volume 18, No. 39, November 3, 1989. The National
Institute on Deafness and Other Communication Disorders (NIDCD) was
inadvertently omitted from the list of participating Institutes. The contact
person for NIDCD is the following:
Vol. 19, No. 2, January 12, 1990 - Page 6
Dr. Ralph F. Naunton
Acting Director, Extramural Programs
National Institute on Deafness and
Other Communication Disorders
Federal Building, Room 1C-11
7550 Wisconsin Avenue
Bethesda, Maryland 20892
Telephone: (301) 496-1804
**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. 19, No. 2, January 12, 1990 - Page 7
FULL TEXT OF RFAs FOR ONLINE ACCESS
RFA NUMBER: 90-CA-08
VIRAL ONCOGENESIS AND PATHOGENESIS OF HEPATOCELLULAR CARCINOMA
P.T. 34; K.W. 0715035, 0705025, 0765033, 1002045
NATIONAL CANCER INSTITUTE
APPLICATION RECEIPT DATE: August 3, 1990
LETTER OF INTENT RECEIPT DATE: June 4, 1990
INTRODUCTION
A diverse group of viral agents are etiologically associated
with human viral hepatitis, some of which are also
associated with chronic sequelae which may progress to
primary hepatocellular carcinoma (PHC). Hepatitis B virus
(HBV) is a double-stranded DNA virus which has a worldwide
distribution, and which can be transmitted by contaminated
blood, blood products, or unsterile needles. In addition,
horizontal spread of the virus occurs, particularly among
young children, by contamination of mucous membranes or
small breaks in the skin with contaminated secretions from
infected playmates. Perinatal (vertical) transmission from
HBV-infected mothers to offspring also occurs and is a
particularly important mode of transmission in Asia. HBV
progresses to a chronic infection or chronic carrier state
in 5-10 percent of the adult clinical cases and has been strongly
associated with the etiology of PHC.
The term "non-A, non-B hepatitis virus" (NANBH) describes
viral hepatitis that occurs in the absence of serologic
markers for known hepatotropic agents such as hepatitis A
virus (HAV), HBV, or other viruses such as cytomegalovirus
or Epstein-Barr virus that are associated with
hepatitis-like symptoms. Since the putative agent was not
HAV or HBV, it was termed non-A, non-B hepatitis. Three
epidemiologic forms of human NANBH, which have been called
"blood-transmitted", "coagulation-factor-transmitted", and
"enteric" or "waterborne", have been proposed based on
studies in primate models. NANBH agents cause an acute
hepatitis that is somewhat milder than HBV induced disease;
however, it has been estimated that at least half of the
NANBH infections result in chronic hepatitis, which in turn
results in cirrhosis in approximately 20 percent of these cases.
Chronicity and cirrhosis carry increased risk of PHC. NANBH
is of particular significance in the U.S. since up to 10 percent of
transfusions in the U.S. are thought to result in hepatitis
and more than 90 percent of the transfusion-associated hepatitis in
the U.S. is associated with NANB agents. The
"blood transmitted" form of NANBH, also referred to by some
investigators as hepatitis C virus (HCV), has an RNA genome
and is
the only one of these agents currently associated with
primary hepatocellular carcinoma.
The present Request for Applications (RFA) is for a single
competition with a deadline
of August 3, 1990, for receipt of applications, and June 4,
1990, for receipt of letters of intent. Applications should
be prepared and submitted in accordance with the aims and
requirements described in this RFA document.
BACKGROUND
Although recent success in the in vitro cultivation of HBV
has made mechanistic studies of its involvement in PHC less
intractable, and the development of lines of HBV transgenic
mice may help in the delineation of the role of the host
immune response in this disease, the molecular mechanism(s)
of HBV induction of liver cancer remain unknown. It does
not appear that a viral oncogene exists in HBV, and unique
"hot spots" of viral integration adjacent to cellular
proto-oncogenes have not been demonstrated. In addition,
the possible role of other viral agents and environmental
cofactors, such as alcohol or aflatoxins in PHC, remains to
be established. Thus, it seemed appropriate to convene a
workshop that would focus on gaps in our knowledge about
the etiology and pathogenesis of PHC and encourage new ideas
and approaches to preventing the development of PHC among
HBV chronic carriers throughout the world.
On February 13-15, 1989, an "International Workshop on
Pathogenesis and Prevention of Hepatocellular Carcinoma" was
held in Oahu, Hawaii. Because PHC is a global problem, the
workshop was co-sponsored by the Fogarty International
Center and the National Cancer Institute, in cooperation
with the Cancer Institute of the Chinese Academy of Medical
Sciences and Merck and Company. The goals of the workshop
were to assess the current state of knowledge of the
mechanisms of PHC oncogenesis and pathogenesis, to assess
the possibilities for prevention of this neoplasia and, to
determine whether there were particular research areas that
needed additional emphasis in the form of an RFA or Request
for Proposals to provide support for specific grant-funded
research or for contract-funded resource activities. The
workshop participants identified a number of issues in
oncogenesis relative to both HBV and HCV in which our
knowledge is limited and which require more active
investigation.
RESEARCH GOALS AND SCOPE
The overall thrust of this RFA is to stimulate research on
the human hepatitis viruses associated with liver cancer
(e.g., HBV, NANBH or HCV), and their interactions with
environmental factors (e.g., dietary aflatoxin), and host
factors (chromosomal fragility, immune response) in order to
determine mechanism(s) involved in establishment of chronic
infection, cell transformation, and PHC. Examples of
research objectives would include the following: (i)
development and/or use of sensitive and specific assays for
blood-borne NANBH (HCV) to determine the possible role of
this agent in PHC; (ii) determination of the prevalence of
HBV strains resistant to currently available vaccines and
the role of genetic variation of HBV isolates in this
process; (iii) definition of the role of the HBV X gene in
transformation; (iv) systematic studies of co-carcinogenesis
(viral, chemical, and/or dietary factors) in the development
of PHC in animal models of human cancer (e.g., the
woodchuck); (v) determination, in transgenic animals, of the
oncogenic potential of specific viral gene products; (vi)
determination of the possible role of cellular oncogenes or
anti-oncogenes in PHC; (vii) investigation of the role of
chromosomal abnormalities in susceptibility to PHC; and
(viii) measurement of the host response to individual viral
proteins with the goal of delineating the host response to
different viral antigens in hepatitis-associated
pre-malignant and malignant sequelae.
Where appropriate, collaborative arrangements to facilitate
the achievement of research goals should be considered.
Applications should contain as goals both methodological
development and application to a specific area of HBV or HCV
oncogenesis as well as studies involving possible
synergistic interactions between viruses, alcohol,
aflatoxins, etc.; basic and/or clinical issues are
considered as appropriate subjects for this RFA.
MECHANISM OF SUPPORT
This RFA will use the National Institutes of Health (NIH)
grant-in-aid (RO1). Responsibility for the planning, direction
and execution of the proposed project will be solely that of
the applicant. Except as stated in this RFA, awards will be
administered under PHS grants policy as described in the Public
Health Service Grants Policy Statement, DHHS Publication No.
(OASH) 82-50,000, revised January 1, 1987.
This RFA is a one-time solicitation. Generally, future
unsolicited competing renewal applications will compete as
research project applications with all other investigator-
initiated applications and be reviewed in a standing
Division of Research Grants study section. However, should
the NCI determine that there is a sufficient continuing
program need, NCI may announce a request for renewal
applications.
Approximately $1,000,000 in total costs per year for five
(5) years will be committed to fund
applications that are submitted in response to this RFA.
Actual funding 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 five (5)
years. The earliest feasible start date for the initial
awards will be April 1, 1991. Although this program is
provided for in the financial plans of the National Cancer
Institute (NCI), award of grants pursuant to this RFA
also is contingent upon the availability of funds for this
purpose. Non-profit and for-profit institutions are
eligible to apply. Foreign as well as domestic institutions
are eligible.
REVIEW PROCEDURES AND CRITERIA
REVIEW PROCEDURE
Upon receipt, applications will be reviewed initially by the
Division of Research Grants 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 how well they meet the goals and
objectives of the program as described in the RFA.
Applications which are judged non-responsive will be
administratively inactivated 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 program staff as described in
the INQUIRIES Section.
In cases where the expected number of applications is large
compared to the number of awards to be made, the NIH will
conduct an administrative prereview (triage) to eliminate
those that clearly are not competitive. Those applications
will be withdrawn from further competition and the applicant
and institutional business official will be notified.
Applications that are judged to be both responsive and
competitive will be evaluated in accordance with the
criteria stated below for scientific/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.
REVIEW CRITERIA
Proposals responsive to this competitive solicitation will
be reviewed in accordance with the criteria stated below.
1. Relevance of the proposed research to the aims of the RFA,
i.e., potential for providing insight on the mechanism(s) of
causation of PHC by hepatitis B virus, hepatitis C virus(es)
(NANBH), either alone or in combination with chemicals
and/or other environmental factors.
2. The scientific merit of the proposed approach, including
the adequacy and quality of the methodological approach and
the research design. Familiarity with the proposed
techniques should be demonstrated, e.g., by the presentation
of preliminary data.
3. The expertise and qualifications of the principal
investigator and proposed staff and/or collaborators to
perform the proposed experiments.
4. Documentation of the adequacy of the facilities and
resources.
The review group will examine proposed budgets and recommend
an appropriate budget for each approved application.
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 10/88 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 and the RFA number should be typed on line 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 the time of submission, two (2) additional copies of the
application should also 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 August 3, 1990. If an
application is received after that date, it will be
administratively withdrawn. Also the Division of Research
Grants will not accept any application in response to this
announcement that is the same as one currently being
considered by any other NIH awarding unit.
Animal and human subject approval clearances must be
submitted with the applications to expedite the review
process.
LETTER OF INTENT
Prospective applicants are asked to submit, by June 4, 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. The
letter of intent is of great benefit to the NCI in planning
for the review, although it is not required, is not binding,
and does not enter into the review of subsequent
applications.
The letter of intent should be sent to:
Dr. John S. Cole, III
Program Director
RNA Virus Studies II
Biological Carcinogenesis Branch
Division of Cancer Etiology
National Cancer Institute
Executive Plaza North, Room 540
Bethesda, Maryland 20892
Telephone: (301) 496-1718
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 Dr. Cole at the above address. The
program director welcomes the opportunity to clarify any
issues or questions from potential applicants.
This program is described in the Catalog of Federal Domestic
Assistance No. 13.393, Cancer Cause and Prevention Research.
Awards are under authorization of the Public Health Service
Act, Section 301 (c), Public Law 78-410, as amended; 42
U.S.C. 241; the Small Business Innovation Development Act,
Public Law 97-219, and Section 410 as amended by Public Law
99-158, 42 U.S.C. 285; and administered under PHS grant
policies and Federal Regulations 42 CFR 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.