From: kristoff@GENBANK.BIO.NET (Dave Kristofferson)
Newsgroups: bionet.sci-resources
Subject: NIH Guide, vol. 21, no. 33, pt. 2, 11 September 1992
Date: 15 Sep 92 18:59:07 GMT
Distribution: bionet


$$XID RFA AG9301 AG-93-01 P1O1 *****************************************

GENETIC AND MOLECULAR BASIS OF LONGEVITY

NIH GUIDE, Volume 21, Number 33, September 11, 1992

RFA:  AG-93-01

P.T. 34; K.W. 1002019, 0710010, 0760015, 1002008, 0710030

National Institute on Aging

Letter of Intent Receipt Date:  October 1, 1992
Application Receipt Date:  November 13, 1992

PURPOSE

The National Institute on Aging (NIA) invites applications for R01
grants to support basic research on the genetic and molecular bases of
longevity.  The goals of the Genetic and Molecular Basis of Longevity
Request for Applications (RFA) are to identify genes which promote
longevity and delay the onset of senescence, termed Longevity Assurance
Genes (LAGs), and determine the biochemical functions and molecular
mechanisms of action of these LAGs.  A multidisciplinary approach to
these complex areas of basic research will facilitate the application
of genetic, biochemical and molecular techniques to defining the
genetic and molecular bases of longevity.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This RFA,
Genetic and Molecular Basis of Longevity, is related to the priority
area of aging. Delineation of the genetic and molecular bases of
longevity and senescence will lead to a fundamental understanding of
aging processes and hasten the development of biological-based
intervention strategies to extend the human health span. Potential
applicants may obtain a copy of "Healthy People 2000" (Full Report:
Stock No. 017-001-00474-0 or Summary Report:  Stock No.
017-001-00473-1) through the Superintendent of Documents, Government
Printing Office, Washington, DC 20402-0325, telephone (202) 783-3238.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, for- profit and
non-profit organizations, public and private, such as universities,
colleges, research foundations, hospitals, laboratories, units of State
and local governments, and eligible agencies of the Federal Government.
Applications from domestic institutions may include international
components if the collaborative effort between domestic and foreign
investigators strengthen the research proposal. Applications from
minority individuals and women are encouraged.

MECHANISM OF SUPPORT

The multidisciplinary, highly interactive approach outlined in this RFA
is intended to facilitate and enhance research progress toward
understanding complex problems in aging biology.  This RFA is a
one-time solicitation for research applications.  The total project
period for applications submitted in response to this RFA may not
exceed five years. The anticipated award date for applications
submitted in response to this RFA is July 1, 1993.  Should the NIA
determine that there is sufficient need to continue this research
program, the NIA may announce a request for new competitive and/or
competitive renewal applications related to the Genetic and Molecular
Basis of Longevity in the form of a second RFA.

FUNDS AVAILABLE

The Genetic and Molecular Basis of Longevity research program will be
supported through the traditional research project grant (R01)
mechanism.  Applicants will be responsible for the planning, direction,
and execution of the proposed research projects.  Research applications
from collaborating Principal Investigators at different institutions
are highly encouraged if the combined expertise of the two research
laboratories will facilitate the research progress of both laboratories
and contribute to the overall research goals outlined in this RFA.

The NIA will set aside a total of $2,000,000 for funding research
projects responsive to the Genetic and Molecular Basis of Longevity RFA
in FY 1993 and expects to make eight to ten grant awards.  Although
this research initiative is provided for in the plans of the NIA, the
award of research grants pursuant to this RFA is contingent upon the
availability of appropriated funds in FY 1993 and the receipt of a
sufficient number of responsive applications with high scientific
merit.

RESEARCH OBJECTIVES

Research with several model systems including yeast, nematodes,
drosophila, rats, mice, and cultured human cells has established that
longevity and senescence are, in part, under genetic control.
Identification and characterization of the specific genes that
determine longevity and contribute to aging and senescence in several
species including humans are central to understanding the fundamental
molecular mechanisms that govern aging and senescence.  Moreover,
knowledge of these fundamental mechanisms will guide and hasten the
development of effective prevention and intervention strategies to
extend the human health span.

The only experimental paradigm known to significantly extend the life
span and health span of mammals (mice and rats) is caloric restriction.
The molecular mechanisms responsible for the increased longevity and
postponed senescence in these short-lived mammals are poorly
understood.  Although more complex than the invertebrate models of
aging and senescence, ad libitum fed and calorically restricted rodents
provide excellent models to begin the search for candidate mammalian
LAGs.

The purposes of this RFA are to stimulate research on the fundamental
mechanisms of aging and senescence, to encourage the application of
results obtained from model systems to understanding human longevity,
and to develop intervention strategies to extend human health span
based on increased knowledge of fundamental aging mechanisms.  The
interactive, multidisciplinary approach outlined in this RFA is
designed to focus the use of various model systems, human cells and
cell lines, molecular reagents, and state-of-the-art molecular biology
and biotechnology on this important area of aging biology.  The
development of sophisticated methods for molecular cloning, gene
amplification, targeted gene insertion and disruption, and the
production of germ-line transgenic organisms via molecular genetic
manipulation of embryos or embryonic stem cells have made such an
approach feasible.  Application of these powerful molecular approaches
to aging research will facilitate the identification of candidate LAGs,
allow evaluation of their effects on longevity and health span in
transgenic model systems, and hasten the search for human homologs of
key LAGs.  It is anticipated that such an approach will facilitate and
optimize research progress and hasten the development of
biological-based intervention strategies designed to prevent or delay
human aging processes and thereby extend human health span.

The major objectives of the Genetic and Molecular Basis of Longevity
RFA and research initiative are:

o  Development of molecular and animal resources to investigate the
molecular basis of longevity;

o  Identification of candidate LAGs in appropriate models of aging;

o  Evaluation of candidate LAG effects on longevity and senescence in
appropriate transgenic organisms;

o  Characterization of the regulation of LAG expression at the
molecular level;

o  Characterization of the biological functions of proteins encoded by
LAGs; and

o  Identification of human counterparts of key LAGs in cultured cells.

Appropriate models for the identification of candidate LAGs include:

o  The yeast Saccharomyces cerevisiae;

o  Short- and long-lived strains of the nematode Caenorhabditis elegans
including age mutants;

o  Short- and long-lived strains of Drosophila melanogaster;

o  Short-lived and longer-lived species of mice including Peromyscus;

o  Mice fed ad libitum or calorically restricted diets;

o  Long-lived strains of mice created by selective breeding of
genetically heterogenous founder populations;

o  Transgenic mice bearing candidate LAGs or putative longevity loci;

o  Human cell lines which display differentiated functions and
senescence in vitro; and

o  Mice created from embryonic stem cells selected in vitro for
particular traits or adaptive responses predicted to have potentially
significant effects on longevity and senescence (e.g., enhanced
resistance to oxidative damage, heat shock and other forms of
biological stress).

Investigators wishing to evaluate the effects of candidate LAGs on
mammalian longevity and senescence are encouraged to apply
state-of-the-art transgenic mouse technology, including the use of
homologous recombination for targeted gene transplacement and gene
disruption, to the construction of appropriate transgenic lines of
mice.  Investigators are encouraged to include strategies, including
the establishment of collaborative arrangements, for the identification
and characterization of human homologs or equivalents of candidate LAGs
identified in yeast, invertebrates and mammalian model systems in
applications submitted in response to this RFA.

The development and application of several areas of molecular
technology to these problems in aging biology have been identified as
high priority including:

o  Development of suitable expression vectors and protocols for
introduction and stable expression of targeted gene transplacements and
the incorporation of multigenic DNA fragments in mouse embryonic stem
cells;

o  Development of suitable expression vectors and protocols to achieve
cell-specific expression of candidate transgenes in somatic cells of
young adult and aged mice.

o  Identification and characterization of age-specific promoters and
regulatory molecules which could be used to enhance the expression of
candidate genes in aged organisms; and

o  Identification of inducible promoters which will drive the
expression of transgenes in aged and senescent animals.

The availability of additional animal models would aid in the
identification and evaluation of candidate LAGs.  For example, the
creation of long-lived strains of mice by selective breeding of highly
outbred founder populations and the genetic and molecular
characterization of these strains is an important aspect of this
research initiative.  In addition, the creation and maintenance of
transgenic mouse lines harboring key LAGs will provide another
important animal resource for this and future research initiatives to
define the genetic and molecular basis of longevity.

Several experimental strategies for the identification and evaluation
of candidate LAGs appear to be appropriate for this RFA.  These include
the evaluation of the effects of known genes believed to have the
characteristics of LAGs (for example; SOD, catalase, and LAG1) on
longevity and health span in transgenic organisms, genetic mapping of
candidate longevity loci in long-lived mouse strains, isolation and
characterization of key genes (regulatory and structural) which are
differentially expressed in animals subjected to caloric restriction
compared to ad libitum fed controls, and identification of human
homologs of LAGs using molecular probes isolated from other model
systems.  In addition, experiments to test the effect of candidate
genes on longevity and senescence in transgenic organisms (invertebrate
and vertebrate) is anticipated via targeted gene disruption and
targeted gene transplacement are encouraged.

The research topics listed above should not be interpreted to be the
only experimental approaches to the identification of the genetic and
molecular bases of longevity and senescence.  Additional innovative
approaches applicable to the research goals of this RFA are welcome and
encouraged.

SPECIAL REQUIREMENTS

Applicants are responsible for proposing research projects that will
advance the goals of the Genetic and Molecular Bases of Longevity
research initiative.  Applicants must have access to appropriate animal
and/or cell culture models for aging research and have the necessary
expertise in genetics, molecular biology, cell biology, or biochemistry
to carry out the proposed research projects.

Investigators supported by the Genetic and Molecular Basis of Longevity
Initiative will interact with each other and the NIA Biology of Aging
Program Staff on a regular basis.  The initial meeting of grant
awardees and Biology of Aging Program staff will serve to coordinate
the individual research projects and Principal Investigators (PIs).
Yearly workshops in which grantees and NIA program staff will
participate will be arranged to establish research priorities, review
research progress and experimental difficulties, coordinate ongoing
research, plan future research activities, and discuss new developments
in molecular biology and biotechnology applicable to this research
program.  Travel funds to attend the yearly workshops in the amount of
$2,000 per year are to be included as a line item in each project
budget.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent by
October 1, 1992.  The letter of intent must include the number and
title of this RFA (AG-93-01), a descriptive title of the proposed
project, and the name, address, phone and FAX numbers of the PI and key
personnel. If the application will involve collaborative or consortium
arrangements, the participating institutions must  also be identified.
Although a letter of intent is not binding, and does not enter into the
review of the subsequent application, the letter is requested to
provide an indication to the NIA of the number and scope of
applications to be reviewed.

Additional information related to the goals and scope of this RFA will
be provided to investigators who have submitted a letter of intent.

The letter of intent is to be addressed to:

Dr. Anna M. McCormick
Biology of Aging Program
National Institute on Aging
Gateway Building, Suite 2C231
Bethesda, MD  20892
Telephone:  (301) 496-6402
FAX:  (301) 402-0010 FAX

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for this grant. These forms are available from most
institutional grants and business offices and from the Office of Grant
Inquiries, Division of Research Grants, National Institutes of Health,
Room 449, Westwood Building, 5333 Westbard Avenue, Bethesda, MD
20892-4500.

The title of this RFA, Genetic and Molecular Basis of Longevity, and
the RFA number, AG-93-001, must be typed on line 2a of the face page of
the application form to ensure that it is assigned to the NIA upon
receipt by the Division of Research Grants.  The RFA label available in
the application form PHS 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 does not reach the review committee in
time for review. The page limitation guidelines outlined in the PHS 398
application packet apply to all applications submitted in response to
this RFA.

Submit the signed original of the application, including the Checklist,
and three signed exact photocopies (single-sided) in one package to:

Division of Research Grants
Westwood Building, Room 240
5333 Westbard Building
Bethesda, MD  20892-4500

In addition, one copy must be sent to the NIA Program Official and one
copy must be sent to the NIA Scientific Review Office.  The appropriate
addresses for these individuals are:

Dr. Anna M. McCormick
Chief, Biology Branch
Biology of Aging Program
National Institute on Aging
Gateway Building, Suite 2C231
Bethesda, MD  20892

Dr. Michael Oxman
Chief, Scientific Review Office
National Institute on Aging
Gateway Building, Suite 2C212
Bethesda, MD  20892

Complete applications are due November 13, 1992, and must address all
requirements in the RFA.  Applicants are advised to obtain the
necessary institutional approval for the use of vertebrate animals and
human tissues, as appropriate, prior to the submission of an
application.  Applications received after the receipt date will be
returned to the applicant without review.  The Division of Research
Grants (DRG) will not accept any application in response to this
announcement that is essentially the same as one currently pending
initial review, unless the applicant withdraws the pending application.
The DRG will not accept any application that is essentially the same as
one already reviewed.  This does not preclude the submission of
substantial revisions of applications already reviewed, but such
applications must include an introduction addressing the previous
critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed by DRG staff for
completeness.  Incomplete applications will be returned to the
applicant without further consideration. Applications judged to be
non-responsive to this RFA will be returned, but may be resubmitted as
investigator-initiated research grant applications at the next
application receipt date. Applications may first receive a preliminary
review by a subcommittee of the review panel to establish those
applications deemed to be competitive.  The NIH will withdraw from
further consideration those applications judged to be noncompetitive
and will notify the applicant PI and the institutional official of this
action. Applications judged to be responsive and competitive will be
evaluated for scientific and technical merit by an appropriate ad hoc
peer review group convened by the NIA Office of Scientific Review.  The
second level of review, by the National Advisory Council on Aging,
considers the priorities and special needs of the NIA.

Reviewers will be asked to review the applications considering the
following criteria:  scientific merit, feasibility and relevance of the
proposed project to the overall goals and objectives of the RFA;
proposed techniques and methodologies to achieve the stated research
goals; qualifications, expertise and proposed responsibilities of the
PI and key personnel; scientific plans and timetable for implementing
the proposed research program; and facilities, resources, and
environment available to the PI and co-investigators.  The initial
review group will critically examine the submitted budget and will
recommend an appropriate budget and period of support for each
application.

INQUIRIES

The Program and Grants Management officials welcome the opportunity to
clarify any issues or questions from potential applicants.  Written and
telephone inquiries concerning the objectives and scope of this RFA and
questions as to whether a specific areas of research would be
considered by the NIA as responsive to this RFA are encouraged.

Direct inquires regarding programmatic issues to:

Dr. Anna M. McCormick
Chief, Biology Branch
Biology of Aging Program
National Institute on Aging
Gateway Building, Suite 2C231
Bethesda, MD  20892
Telephone:  (301) 496-6402
FAX:  (301) 402-0010

Direct inquires regarding fiscal matters to:

Mr. Joseph Ellis
Grants Management Officer
Grants and Contracts Management Office
National Institute on Aging
Gateway Building, Suite 2N212
Bethesda, MD  20892
Telephone:  (301) 496-1472

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance
No. 93.866.  Awards are made under the authorization of the Public
Health Service Act, Title IV, Part A (Public Law 99-158, 42 USC 241 and
285) and administered under PHS grants policies and Federal Regulations
42 CFR 52 and 45 CFR Part 74. This program is not subject to the
intergovernment review requirements of Executive Order 12372 or Health
Systems Agency review.


$$XID RFA CANR9227 CA/NR/92-27 P1O1 ************************************

QUALITY OF LIFE ASSESSMENT IN SPECIAL POPULATIONS

NIH GUIDE, Volume 21, Number 33, September 11, 1992

RFA:  CA/NR-92-27

P.T. 34; K.W. 0730070, 0414014, 0413001, 0414013, 0785035

National Cancer Institute
National Center for Nursing Research

Letter of Intent Receipt Date:  October 23, 1992
Application Receipt Date:  January 19, 1993

PURPOSE

The Division of Cancer Prevention and Control (DCPC) of the National
Cancer Institute (NCI) and the National Center for Nursing Research
(NCNR) invite grant applications (R01s) to develop methods for
assessing global health-related quality of life (QOL) or specific QOL
dimensions such as physical symptoms (including pain), functional
status, psychological function, and social interactions in cancer
patients from diverse sociocultural backgrounds.

Limited availability of methods that are sensitive to needs of patients
from special populations has restricted the inclusion of these groups
in clinical studies with these endpoints and has hampered understanding
of symptom control and supportive care in these patients.  This Request
for Applications (RFA) provides support for the development or
adaptation, validation, and pilot testing of techniques for measuring
health-related quality of life or specific QOL dimensions in patients
from culturally diverse backgrounds.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This RFA,
Methodologic Approaches to Quality of Life/Psychosocial Assessment in
Special Populations, is related to the priority area of cancer.
Potential applicants may obtain a copy of "Healthy People 2000" (Full
Report:  Stock No. 017-001-00474-0 or Summary Report: Stock No.
017-001-00473-1) through the Superintendent of Documents, Government
Printing Office, Washington, DC 20402-9325, telephone 202-783-3238.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, for-profit and
non-profit, public and private organizations, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal Government.
Applications from minority individuals and women are encouraged.

MECHANISM OF SUPPORT

Support of this program will be through the National Institutes of
Health (NIH) traditional research project grant (R01).  Applicants will
be responsible for the planning, direction, and execution of the
proposed project. The total project period for applications submitted
in response to this RFA should not exceed three years. In addition to
the requirements 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) 90-50,000, (rev. 10/90).

This RFA is a one-time solicitation.  Future unsolicited competitive
continuation applications will compete with all other
investigator-initiated research grant applications and be peer reviewed
by a chartered study section in the Division of Research Grants (DRG),
NIH.  However, should the NCI or the NCNR determine that there is a
sufficient continuing program need, a request for competitive
continuation applications will be announced.  Only recipients of awards
under this RFA will be eligible to apply.

FUNDS AVAILABLE

Total costs of $1,600,000 per year for three years will be committed to
specifically fund applications that are submitted in response to this
RFA.  It is anticipated that four to eight awards will be made.  This
funding level is dependent upon the receipt of a sufficient number of
applications of high scientific merit.  The earliest feasible start
date for the initial awards will be September 1, 1993.  Although this
program is provided for in the financial plans of the NCI and the NCNR,
the award of grants pursuant to this RFA is also contingent upon the
availability of funds for this purpose.

RESEARCH OBJECTIVES

Background

The concept of health-related QOL as an important aspect of medical
decision-making has evolved during the last decade, as patients and
health care providers have become more aware of the impact of treatment
on quality of survival (Aaronson et al., 1989; Spilker, 1990).  The
United States Food and Drug Administration has recognized benefit to
QOL (as well as improved survival) as a basis for approval of new
anticancer drugs (Johnson and Temple, 1985), and QOL endpoints are
often included as endpoints in clinical trials along with the
traditional endpoints of tumor response, survival, and toxicity
(Moinpour et al., 1989; Skeel, 1989).

Many instruments for assessing health-related QOL and specific domains
of physical symptoms, functional status, psychological function, and
social interactions have been developed and validated for cancer
patients (Cella and Tulsky, 1990).  However, few existing methods are
appropriate for patients from diverse cultural backgrounds. This
compounds the practical difficulties of language barriers, cultural
differences, and economic constraints in accrual of minority and
medically underserved patients to clinical trials in cancer treatment
and supportive care. As a result, decisions regarding treatment and
supportive care for patients from special populations are often based
on clinical research that includes few participants from these groups.
QOL and symptom control are important considerations in patients from
special populations because many cancers are diagnosed at later stages
or have poorer prognosis in these groups.

A small number of instruments for QOL assessment and symptom
measurement (eg., pain) are available in languages other than English.
However, while language is the most obvious barrier to assessment,
simple translation of standardized instruments is an inadequate
solution to this problem.  Psychosocial concepts do not necessarily
have a one-to-one correspondence from language to language or, within
a language, from dialect to dialect.  Techniques for measuring
health-related quality of life must be sensitive to these subtle
language differences, as well as to cultural differences that influence
understanding of QOL constructs.  Thus development or modification of
QOL instruments for use in these groups requires knowledge of the
customs, beliefs, and traditions that the patient and family practice
in relation to medication, response to illness, and sense of
independence, in addition to linguistic expertise.  Methods or
instruments must be validated carefully in the target population to
ensure that the adapted QOL concept has the same meaning as in its
original language and culture.  This may involve iterative forward and
backward translations and/or extensive cross-validation studies.

Education level and socioeconomic status are important considerations
in QOL measurement.  For example, culturally sensitive translation of
self-administered questionnaires may be inadequate for patients with
low literacy skills, while telephone interview methods may
systematically exclude indigent patients who do not have telephone
service.

Research Goals and Scope

The goal of this RFA is to foster development or adaptation of methods
for assessing health-related quality of life in cancer patients from
diverse sociocultural backgrounds, for application in cancer prevention
and treatment clinical trials and in supportive care research.

Applications must focus on development, validation, and pilot testing
of methods to assess health-related quality of life and/or its many
aspects in culturally diverse populations.  Objectives include:

o  To develop or adapt existing methods for assessing aspects of QOL in
cancer patients from special populations that are sensitive to (a)
language and dialect; (b) customs, beliefs, and traditions; and (c)
education and socioeconomic status;

o  To validate methods in the target population:  general
acceptability, reproducibility, construct validity, and responsiveness
to change; and

o  To demonstrate applicability of the assessment methods in pilot
studies of cancer treatment or supportive care interventions in the
target population.

For the purposes of this RFA, special populations include Hispanic
Americans, Black Americans, low socioeconomic status groups, and
persons with low literacy skills.  Population subgroups may be
identified by geographic or cultural criteria.  Other smaller minority
or ethnic groups, such as Native Americans, may be considered if
investigators can demonstrate (1) specific need for QOL assessment
tools in the group; (2) a significant cancer burden in the group; and
(3) immediate applications for the instrument/method in cancer
treatment and cancer control research in the group.

Applicants will develop or adapt existing methods for assessing global
health-related QOL and/or various components for use in patients from
diverse cultural backgrounds.  When feasible, adaptation of existing
instruments or methodology for use in special populations is preferred,
to facilitate inclusion of minority patients in cooperative group
clinical trials and to allow cross-cultural comparisons.

Simple translation of standardized instruments is not an adequate
response to this RFA.  Psychosocial concepts such as emotional function
are particularly difficult to convey in translation, requiring
attention to dialect and subtle details of inflection and word
meanings.  Also, QOL expectations may differ among diverse
sociocultural groups, and QOL constructs may not have a one-to-one
correspondence across these groups.  Thus careful validation is
important to ensure that the translated QOL concept has the same
meaning as in its original language and that it is sensitive to the
customs, beliefs, and traditions of the target population.  This may
require complex procedures, such as  series of iterative forward and
backward translations, or extensive cross-validation studies with
established scales in the translated language as well as between
translated and original versions of the instrument.

Techniques should focus on measuring global health-related QOL or
specific domains or aspects of QOL, such as functional status, disease-
and/or treatment-related symptoms, emotional or psychological
functioning, and social functioning and support.  Applications should
focus on methods to evaluate within-person change over time (i.e.,
evaluative versus discriminative or predictive approaches).

General acceptability of the QOL assessment method must be evaluated in
patients from the target population. Psychometric validation must
include demonstration of reproducibility (replicability), construct
validity (correlation with expected changes in variables usually used
to measure the construct), and responsiveness (ability to demonstrate
a difference over time when one exists) within the study population.
Implementation issues, including ease of administration and respondent
burden, should be addressed, and appropriateness for the educational
level and socioeconomic status of the target population should be
demonstrated.

Applicability of methods developed through this initiative must be
demonstrated by pilot testing in a clinical research project.  The
instrument or technique may be included as a QOL endpoint in a cancer
treatment clinical trial or, with other standard measures, as a outcome
variable in clinical studies of supportive care or cancer
rehabilitation interventions.  To this end, investigators are
encouraged to collaborate with clinical oncology staff in the
NCI-funded Community Clinical Oncology Program (CCOP) network, NCI-
designated Clinical or Comprehensive Cancer Centers, NCI- sponsored
Clinical Cooperative Groups, or university-based oncology programs that
actively participate in clinical cancer research.  Implementation
should follow NCI guidelines for QOL research in cancer clinical trials
(Nayfield et al, 1991; Gotay et al., 1992), and methods of
administration, timing, quality control, and data analysis should be
addressed in the pilot study.  The spectrum of potential applications
in clinical trials and research on psychosocial aspects of cancer
should also be identified.

Priority will be given to applications that comprise a broad program of
methods development rather than those that develop/adapt a single tool
for one population subgroup.  For example, applicants are encouraged to
adapt an assessment method that provides a global QOL assessment as
well as subscores for specific constructs or domains; to focus on use
of an instrument or method in several related population subgroups; to
highlight development/adaptation of a spectrum of instruments for one
special population; or to include development/adaptation of predictive
methods to enhance application of the evaluative methods.

A multidisciplinary approach is recommended, including
psychometricians; ethnologists, medical anthropologists, and others
experienced in health care delivery to special populations; expertise
in comparative and geographical linguistics, education, and literacy;
social workers, psychologists, or psychiatrists; clinical oncology
(nursing, medical oncologists, oncologic surgeons); and experience in
clinical trials research.  Collaboration with an established cancer
clinical trials network for pilot testing is encouraged.

STUDY POPULATIONS

SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION
OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES
IN CLINICAL RESEARCH STUDY POPULATIONS

NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements are required to include
minorities and women in study populations so that research findings can
be of benefit to all persons at risk of the disease, disorder or
condition under study; special emphasis must placed on the need for
inclusion of minorities and women in studies of diseases, disorders and
conditions which disproportionately affect them.  This policy is
intended to apply to males and females of all ages.  If women or
minorities are excluded or inadequately represented in clinical
research, particularly in proposed population- based studies, a clear
and compelling rationale must be provided.

The composition of the proposed study population must be described in
terms of gender and racial/ethnic group.  In addition, gender and
racial/ethnic issues must be addressed in developing a research design
and sample size appropriate for the scientific objectives of the study.
This information must be included in the form PHS 398 (rev. 9/91) in
Sections 1-4 of the Research Plan AND summarized in Section 5, Human
Subjects.

Applicants are urged to assess carefully the feasibility of including
the broadest possible representation of minority groups.  However, the
NIH recognizes that it may not be feasible or appropriate in all
research projects to include representation of the full array of United
States racial/ethnic minority populations [i.e., Native Americans
(including American Indians or Alaskan Natives), Asian/Pacific
Islanders, Blacks, Hispanics].  The rationale for studies on single
minority population groups should be provided.

For the purpose of this policy, clinical research is defined as human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but not limited to clinical trials.

The usual NIH policies concerning research on human subjectsalso apply.
Basic research or clinical studies in which human tissues cannot be
identified or linked to individuals are excluded.  However, every
effort should be made toinclude human tissues from women and
racial/ethnic minorities when it is important to apply the results of
the study broadly, and this should be addressed by applicants.

For foreign awards, the policy on inclusion of women applies fully;
since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States' populations, including
minorities.

If the required information is not contained within the application,
the application will be returned.

Peer reviewers will address specifically whether the Research Plan in
the application conforms to these policies.  If the representation of
women or minorities in a study design is inadequate to answer the
scientific question(s) addressed AND the justification for the selected
study population is inadequate, it will be considered a scientific
weakness or deficiency in the study design and will be reflected in
assigning the priority score to the application.

All applications for clinical research submitted to the NIH are
required to address these policies.  NIH funding components will not
award grants or cooperative agreements that do not comply with these
policies.

LETTER OF INTENT

Each prospective applicant is asked to submit, by October 23, 1992, a
letter of intent that includes a descriptive title of the proposed
research; the name, address, telephone and FAX numbers of the Principal
Investigator (PI); the names of other key personnel; the participating
institution(s); 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 a subsequent application, it contains
information that is helpful in planning for the review.  The letter of
intent allows NCI and NCNR staff to estimate the potential review
workload and helps to avoid conflict of interest in the review.
The letter of intent is to be sent to:

Susan G. Nayfield, M.D., M.Sc.
Program Director
Community Oncology and Rehabilitation Branch
Division of Cancer Prevention and Control
National Cancer Institute
Executive Plaza North, Suite 300
Bethesda, MD  20892**
Telephone: (301) 496-8541
FAX:  (301) 496-8667

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  The application package is available at
most institutional business offices; from the Office of Grants
Inquiries, Division of Research Grants, National Institutes of Health,
Westwood Building, Room 449, Bethesda, MD  20892, telephone
301-496-7441; and from the NCI and NCNR Program Directors named above.

The RFA label available in the application form PHS 398 must be affixed
to the bottom of the face page of the application.  Failure to use this
label could result in delayed processing of the application such that
it may not reach the review committee in time for review.  In addition,
the RFA number and title must be typed on line 2a of the face page of
the application form and the YES box must be marked.

Submit a signed, typewritten original of the application, including the
Checklist, and three signed, exact photocopies, in one package to the
DRG at the address below. The photocopies must be clear and
singlesided.

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

At the time of submission, two additional copies of the application
must be sent to:

Referral Officer
Division of Extramural Activities
National Cancer Institute
Westwood Building, Room 838
Bethesda, MD  20892

If the applicant has an approved assurance covering the research, the
applicant should provide with the application certification of
Institutional Review Board (IRB) approval if humans are involved.
These reviews and approvals should occur prior to submission of the
application for award and the certifications should be submitted with
the application. If humans will be subjects of the research at
performance sites other than the applicant organization, the applicant
must identify, in the application, the assurance status of each
participant.  Failure to provide required certifications in the
application could result in delay of an award. Instructions regarding
inclusion of human subjects are given on pages 22-23 and 25-26 of PHS
398 (rev. 9/91).

Applications must be received by January 19, 1993.  If an application
is received after that date, it will be returned to the applicant.  The
DRG will not accept any application in response to this announcement
that is essentially the same as one currently pending initial review,
unless the applicant withdraws the pending application.  The DRG will
not accept any application that is essentially the same as one already
reviewed.  This does not preclude the submission of a substantial
revision to an already reviewed application, but such an application
must include an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Review Procedure

Upon receipt, applications will be reviewed initially by the DRG for
completeness.  An incomplete application will be returned to the
applicant without further consideration. Evaluation for responsiveness
to the RFA is an NCI and NCNR 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 judged non-
responsive will be returned, but may be submitted as
investigator-initiated research grant applications at the next regular
receipt date.  Questions concerning the relevance of proposed research
to the RFA should be directed to the Program Director as described
below.

If the number of applications is large compared to the number of awards
to be made, the NCI and NCNR may conduct a preliminary scientific peer
review to triage applications on the basis of relative competitiveness
and to eliminate those applications that are clearly not competitive.
The NCI and NCNR will withdraw from further 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 according to the review criteria stated 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 for NCI and the
National Advisory Council for NCNR will consider the special needs of
the NCI and the NCNR and the priorities of the National Cancer Program.

Review Criteria

Applications responsive to this competitive solicitation will be
reviewed in accordance with the criteria stated below:

o  Scientific merit of the project design and feasibility of the
proposed methods for:  (a) developing/adapting QOL assessment measures
for use in special populations; (b) validating the instruments or
methods in the target population; and (c) pilot testing the instruments
in the clinical research setting;

o  Appropriateness of the study population to the goals and objectives
of the RFA, and investigator access to the study population.

o  Potential for application of newly-developed QOL assessment
techniques within ongoing NCI-sponsored or comparable clinical research
programs;

o  Experience, commitment, and leadership ability of the PI for the
research project; inclusion of medical or nursing professionals in both
oncology and psychology/psychiatry at the leadership level; and
qualifications and experience of other members of the research team to
participate in the proposed project;

o  Availability and proposed use of multidisciplinary expertise from
related fields of psychometrics, linguistics, ethnology, medical
anthropology and sociology, epidemiology, and health services research,
and QOL or other medical outcomes assessment.

o  Adequacy of existing or proposed facilities, equipment and
resources;

o  Adequacy of the proposed means for protecting against hazardous or
unethical research procedures; and

o  Appropriateness of the requested budget and timetable for completion
relative to the proposed research.

The review group will critically examine the submitted budget and will
recommend an appropriate budget and period of support for each scored
application.  Allowable direct costs for the project will NOT include
payment for services and procedures that are a routine part of cancer
treatment and patient care.  Expenses incurred in the development or
adaptation of instruments (including translation) and validation are
allowable costs.  For pilot testing, QOL data collection and analysis
costs are allowable; however, other expenses for the clinical research
project in which pilot testing occurs are excluded.

Annual budgets should include travel funds for the PI and
co-investigators to one two-day meeting in Bethesda, MD, to facilitate
review of progress with program staff and to foster sharing of work in
progress with other researchers.

AWARD CRITERIA

The following factors will be considered in making final decisions:
(1) the scientific merit of the proposed project as determined by peer
review; (2) availability of funds; and (3) program balance among
research areas of the RFA.

INQUIRIES

Written and telephone inquiries concerning the objectives and scope of
this RFA, or inquiries about whether specific proposed research would
be responsive, are encouraged and should be directed to the Program
Directors at the addresses provided below.  The Program Directors
welcome the opportunity to clarify any scientific or programmatic
issues or questions from potential applicants.

For the National Cancer Institute:

Susan G. Nayfield, M.D., M.Sc.
Program Director
Community Oncology and Rehabilitation Branch
Division of Cancer Prevention and Control
National Cancer Institute
Executive Plaza North, Suite 300
Bethesda, MD  20892
Telephone:  (301) 496-8541
FAX:  (301) 496-8667

For the National Center for Nursing Research:

Martha Ann Carey, Ph.D., R.N.
Health Promotion/Disease Prevention Branch
National Center for Nursing Research
Westwood Building, Room 757
Bethesda, MD  20892
Telephone:  (301) 402-3296
FAX: (301) 402-2402

Written and telephone inquiries of a budgetary, administrative, and/or
policy nature to:

Ms. Eileen M. Natoli
Grants Management Team Leader
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Suite 242
Bethesda, MD  20892
Telephone:  (301) 496-7800
FAX:  (301) 496-8601

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance
No. 93.399, Cancer Control Research, and 93.361, Nursing Research.
Awards are made under the authorization of the Public Health Service
Act, Title IV, Part A (Public Law 78-410, as amended by Public Law
99-158, 42 USC 241 and 285) and administered under PHS grants 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.

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Gotay CC, Korn EL, McCabe MS, et al.  Building quality of life
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Holland JC, Rowland JH, eds.  Handbook of Psychooncology: Psychologic
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