From: kristoff@GENBANK.BIO.NET (Dave Kristofferson)
Newsgroups: bionet.sci-resources
Subject: NIH Guide, vol. 21, no. 30, pt. 3, 21 August 1992
Date: 21 Aug 92 19:18:28 GMT
Distribution: bionet


$$XID RFA CANR9226 CA/NR-92-26 P1O1 ************************************

INTERVENTIONS TO ENHANCE ADJUSTMENT TO CANCER RISK OR DIAGNOSIS

NIH GUIDE, Volume 21, Number 30, August 21, 1992

RFA:  CA/NR-92-26

P.T. 34; K.W. 0414014, 0715035, 0745020, 0411005

National Cancer Institute
National Center for Nursing Research

Letter of Intent Receipt Date:  September 18, 1992
Application Receipt Date:  December 8, 1992

PURPOSE

The Division of Cancer Prevention and Control (DCPC) of the National
Cancer Institute (NCI) and the National Center for Nursing Research
(NCNR) invite investigator-initiated grant applications for
psychosocial research directed at improving quality of life and
increasing compliance with treatment regimen of cancer patients or
adherence to early detection practices of persons at high risk of
cancer.

The goal of this Request for Applications (RFA) is to enhance the
quality of life of cancer patients and persons at increased risk of
cancer through effective psychosocial counseling early in the natural
history of disease, i.e., at identification of increased risk,
diagnosis of cancer, or initiation of cancer treatment.  The intent of
this effort is to invite research applications that evaluate the
efficacy of specific counseling interventions in improving quality of
life and increasing medical compliance in defined patient populations
or improving quality of life and increasing adherence to early
detection programs in persons notified of increased cancer risk.

Applications must also evaluate timing, content, and structure of the
counseling intervention and characteristics of patients with most need
of and benefit from the intervention.  In addition, the potential for
community implementation, effectiveness in the community setting, and
costs of services and payment mechanisms for the intervention under
study must be addressed.

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,
Interventions to Enhance Adjustment to Cancer Risk or Diagnosis, 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 may not exceed four years.  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,
revised October 1, 1990.

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 $2,400,000 per year for four years will be committed to
fund applications submitted in response to this RFA.  It is anticipated
that five to six 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 July 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

A.  Background

While psychosocial support is recognized as an integral aspect of
cancer care, especially in the context of survivorship, complex issues
of counseling and support early in the natural history of disease have
not been adequately addressed.  Psychotherapeutic interventions,
pharmacologic management, behavioral techniques, and self-help and
mutual support programs are offered to many patients under the premise
that doing something is better than doing nothing; yet scientific
evaluation of the efficacy of these different approaches is often
lacking.  In addition, little information is available regarding
optimal timing, content, or structure of these interventions,
especially during phases of early detection, diagnosis, and initial
treatment.

As current health care practice emphasizes disease prevention, many
persons learn of their increased risk of cancer as part of a general
risk assessment, from results of routine screening procedures or at the
time of a relative's diagnosis.  Many cancer prevention clinical trials
recruit persons at high risk of disease, making potential participants
aware of their risk status as an eligibility criterion.  The potential
psychological impact and ethical implications of risk assessment and
notification are beginning to be recognized (Lerman et al., 1991),
especially for cancers in which primary prevention strategies are yet
unproven.

For many persons at increased risk of cancer, the knowledge of
increased risk and fear of developing disease may impact on health
behavior, particularly on early detection practices.  While too little
fear and anxiety of disease may promote denial of risk, too much may
lead to avoidance of screening altogether.  For example, while a family
history of breast cancer and perceived vulnerability to the disease
have been associated with repeat participation in mammography
screening, anxiety may reduce the likelihood of adherence to
mammography recommendations on a regular basis (Lerman et al., 1990).
Although Kash et al. (1992) found high attendance at
regularly-scheduled mammography among women with a strong family
history of breast cancer, higher levels of anxiety were directly
related to decreased frequency of clinical breast examination and
performance of breast self-examination.  More than 27 percent of women
in this latter study had psychologic distress consistent with the need
for counseling.

For patients newly-diagnosed with cancer, but for whom cure or
prolonged survival are realistic expectations, early psychosocial
adjustment is equally as important as physiological functioning.
Cancer-directed therapy for these patients is often intense and
frequently involves a multidisciplinary approach.  Acute side effects
of treatment may dramatically alter physical appearance, self image,
daily functioning, and other domains of quality of life, to the point
that patients may become discouraged and fail to complete an initial
treatment program.  As compliance with treatment regimen is an
important determinant of outcome for many primary cancer sites
(Bonnadonna and Valagussa, 1981; Taylor et al., 1985; Richardson et
al., 1990), early psychologic adjustment has the potential to impact on
response to therapy and overall survival, as well as to improve the
general quality of life during initial treatment.

B.  Research Goals and Scope

This initiative promotes research to develop, implement, and evaluate
the efficacy and/or effectiveness of specific psychosocial counseling
interventions on the quality of life of persons notified of increased
cancer risk or newly-diagnosed cancer patients with good prognosis.

Objectives comprise:

(1) To evaluate the efficacy of specific counseling interventions in
high risk individuals or newly- diagnosed cancer patients in (a)
improving quality of life and (b) enhancing compliance with treatment
regimen or adherence to early detection practices.

(2) To identify characteristics of successful interventions.  For
counseling programs: timing, content, and structure; for study
populations:  subgroups with greatest need and greatest benefit.

(3) To assess the potential for community implementation:
effectiveness in the community setting, costs, and payment mechanisms.

The goal of this RFA is to evaluate the efficacy of specific counseling
interventions in defined patient populations.  To this end, a study
design including random allocation to control and intervention groups
is preferred.  However, randomization at the level of physician
practices, clinics, hospitals, or communities (rather than of
individual patients) may be necessary to avoid selection bias or
contamination effects.  A quasi-experimental design may be considered
if randomization is not possible and if this approach provides
reasonable assessment of efficacy.

A major objective of this RFA is to determine the impact of the
intervention on quality of life and adherence/compliance.  Outcome
variables must include standard measures of health-related quality of
life and/or specific quality of life domains.  Assessment instruments
must have demonstrated reproducibility, validity, and responsiveness;
methods must be sensitive to specific needs of the study population and
appropriate for its educational and social background.  Adherence and
compliance must be determined by accepted health services techniques.
Intermediate endpoints of psychologic and/or physiologic measurements
may be included if they support the study hypothesis but may not be the
focus of the research application.  Cancer detection rates in high risk
populations and survival times or rates for newly diagnosed cancer
patients are beyond the scope of this research.

For purposes of this RFA, psychosocial counseling is defined as
short-term, time-limited therapy that addresses not only the emotional
and adjustment issues of coping with the risk or diagnosis of cancer,
but also issues such as the need to comply with early detection
guidelines or initial treatment plans and medical follow-up.  Examples
of interventions include informal self-help or mutual support groups,
behavioral interventions (such as coping strategies or relaxation
techniques), and more intensive individual counseling by psychiatrists
and psychologists.  Psychopharmacologic interventions may be evaluated
as adjunctive therapy to counseling components; applications that
include pharmacologic interventions as the only approach (e.g.,
clinical trials of psychotropic drugs) will be considered unresponsive
to the RFA.

Applications may incorporate existing but previously untested
interventions, adapt existing programs for specific patient groups, or
develop new counseling interventions.  The components of the proposed
counseling intervention must be described clearly in the research
application.  In addition to efficacy, evaluations of the intervention
must assess the timing, content, and structure of the counseling
program and identify characteristics of patients with most need of and
benefit from the intervention.

Interventions must target either of the following populations:

(1) Persons notified of increased risk of cancer(s) for which primary
prevention strategies are yet unproven, but for which early detection
is effective.  Examples of "risk-notified" persons include, but are not
limited to, women at increased risk of breast cancer due to family
history, reproductive history, or atypical hyperplasia on breast
biopsy; women with cervical dysplasia on pap smear; persons with a
family history of colon cancer and multiple colon polyps; and older men
with a family history of prostate cancer.

(2) Newly-diagnosed cancer patients with reasonable chance of cure or
prolonged survival with state-of- the-art therapy.  Examples include,
but are not limited to, patients with Hodgkin's disease, early stage
breast cancer, testicular cancer, ovarian cancer, and early stage
prostate cancer.

For applications that evaluate the efficacy of a counseling
intervention in the research setting (e.g., university cancer centers),
investigators must also evaluate the potential for transfer of the
intervention technology into the community setting.  This includes
assessing the efficiency of the intervention with respect to use of
community resources, and considerations of cost of the counseling
services and mechanisms of payment or reimbursement.  Investigators
testing counseling interventions in community practice settings must
address the potential for dissemination into diverse community
practices, as well as costs and payment mechanisms.

A multi-disciplinary approach including expertise in cancer prevention,
clinical oncology, psychiatry/psychology, nursing, social work,
epidemiology, and health services research is recommended.

C.  References

Bonadonna G, Valagussa P.  Dose-response effect of adjuvant
chemotherapy in breast cancer.  N Engl J Med 304:10-46, 1981.

Broadhead WB, Kaplan BH, James SA, et al.  The epidemiologic evidence
for a relationship between social support and health.  Am J Epidemiol
117:521-37, 1983.

Cohen J, Cullen JW, Martin LR, eds.  Psychosocial Aspects of Cancer.
New York, Raven Press, 1982.

Holland JC, Rowland JH, eds.  Handbook of Psychooncology: Psychologic
Care of the Patient with Cancer.  New York, Oxford University Press,
1989.

Institute of Medicine.  Effectiveness and Outcomes in Health Care.
Washington, DC, National Academy Press, 1990.

Kash KM, Holland JC, Halper MS, Miller DG.  Psychologic distress and
surveillance behaviors of women with a family history of cancer.  J
Natl Cancer Inst 84:24-30, 1992.

Lerman C, Rimer BK, Trock B, et al.  Factors associated with repeat
adherence to breast cancer screening.  Prev Med 19:279-290, 1990.

Lerman C, Rimer BK, Engstrom PF.  Cancer risk notification:
Psychosocial and ethical implications.  J Clin Oncol 9:1275-1282, 1991.

Osoba D, ed.  Effect of Cancer on Quality of Life.  Boca Raton, FL, CRC
Press, Inc., 1991.

Richardson JL, Shelton DR, Krailo M, et al.  The effect of compliance
with treatment on survival among patients with hematologic
malignancies.  J Clin Oncol 8:356-364, 1990.

Taylor SE, Lichtman RR, Wood JV, et al.  Illness-related and
treatment-related factors in psychologic adjustment to breast cancer.
Cancer 55:2506-13, 1985.

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 subjects also
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 to include 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 September 18, 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; 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.  It allows NCI
and NCNR staff to estimate the potential review workload and 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

*The mailing address given is the ZIP code 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 of Executive Plaza North is:  6130
Executive Boulevard, Rockville, Maryland  20852.

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, Maryland 20892, telephone
301-496-7441; and from the NCI Program Director 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
address below.  The photocopies must be clear and single sided.

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.
Reviews and approval should occur prior to submission of the
application for award and the certification 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 close of business December 8, 1992.
If an application is received after that date, it will be returned to
the applicant.  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 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 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 to the applicant, but may be submitted
as investigator-initiated research grant applications at the next
receipt date.  Questions concerning the relevance of proposed research
to the RFA should be directed to the Program Directors as described in
INQUIRIES.

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 the 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 the NCI and
the National Advisory Council for the NCNR will consider the special
needs and the research priorities of the Institute and Center.

B.  Review Criteria

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

o  Scientific merit of the research project design for the proposed
intervention, including selection of outcome measures and the
feasibility of the procedures to be used.

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

o  Appropriateness of the counseling intervention to the goals and
objectives of the RFA, and the potential for evaluating the efficacy of
the intervention in the study population.

o  Potential for identifying characteristics of successful counseling
interventions and for extending successful interventions into the
community setting.

o  Experience, commitment, and leadership ability of the Principal
Investigator for the research project; inclusion of professionals in
oncology, psychiatry, psychology, and nursing at the leadership level;
and qualifications and experience of other members of the research team
to participate in the proposed study.

o  Availability and proposed use of multidisciplinary expertise from
related fields of epidemiology, behavioral and social sciences, health
services evaluation, and specialized health care professionals as
appropriate for the focus of the proposed research.

o  Adequacy of existing and proposed facilities.

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

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 intervention will NOT
include payment for cancer screening tests and procedures that are a
routine part of cancer treatment and patient care.  Expenses incurred
in development and implementation of the proposed research, including
baseline and follow-up surveys, design of materials, and professional
education, are allowable costs.

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

AWARD CRITERIA

The following factors will be considered in making funding decisions:

o  scientific merit of the proposed project as determined by peer
review
o  availability of funds
o  program balance among research areas of the RFA

INQUIRIES

Written and telephone inquiries concerning the objectives and scope of
this RFA and inquiries about whether or not specific proposed research
would be responsive, are encouraged and should be directed to the
Program Directors at the addresses provided below.  Program Directors
welcome the opportunity to clarify any scientific and programmatic
issues or questions from potential applicants.

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

or

Laura A. James, R.N., Ph.D.
Nurse Scientist Administrator
Acute and Chronic Illness Branch
National Center for Nursing Research
Westwood Building, Room 754
Bethesda, MD  20892
Telephone:  (301) 496-0523
FAX:  (301) 402-2402

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

Mrs. 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.


$$XID RFA AI9211 AI-92-11 P1O1 *****************************************

THE EFFECTS OF SILICONE ON THE IMMUNE RESPONSE

NIH GUIDE, Volume 21, Number 30, August 21, 1992

RFA:  AI-92-11

P.T. 34; K.W. 0710070, 0740070, 0715015

National Institute of Allergy and Infectious Diseases
National Institute of Arthritis and Musculoskeletal and Skin Diseases

Letter of Intent Receipt Date:  September 15, 1992
Application Receipt Date:  November 20, 1992

PURPOSE

The Division of Allergy, Immunology and Transplantation (DAIT) of the
National Institute of Allergy and Infectious Diseases (NIAID) and the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) invite applications for studies focused on the short- and long-
term effects of silicone polymers and their breakdown products on the
cellular and molecular components of the immune system and its
functions and how these changes might contribute to the initiation of
self-reactivity and the induction of autoimmune disease.

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 Request
for Applications (RFA), The Effects of Silicone on the Immune Response,
is related to the priority area of diabetes and chronic disabling
conditions.  Potential applicants may obtain a copy of "Healthy People
2000" (Full Report:  Stock No. 017-001-00474-0) or "Healthy People
2000" (Summary Report:  Stock No. 017-001-00473-1) through the
Superintendent of Documents, Government Printing Office, Washington, DC
20402-9325 (telephone 202-782-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by public and private, foreign and
domestic, for-profit and non-profit organizations, public and private,
such as universities, colleges, hospitals, laboratories, units of State
and local governments, and eligible agencies of the Federal Government.
Women and minority investigators are encouraged to apply.  Foreign
institutions are not eligible to apply for the First Independent
Research Support and Transition (FIRST) Award.

MECHANISM OF SUPPORT

The mechanisms of support for this program will be the research project
grant (R01) and the FIRST Award (R29).  The regulations (CFR Title 42,
Part 52 and, as applicable to State and local governments, Title 45,
Part 74) and policies that govern the research grant programs of the
National Institutes of Health will prevail.  Responsibility for the
planning, direction, and execution of the proposed project will be
solely that of the applicant.  The total project period may not exceed
five years.  The earliest anticipated award date will be July 1, 1993.

This RFA is a one-time solicitation.  Future competing continuation
applications will be considered unsolicited and compete with all
investigator-initiated applications and will be reviewed according to
the customary NIH peer review procedures.

FUNDS AVAILABLE

Up to $650,000 total costs for the first-year and additional approved
expenses for up to five years, has been committed to fund applications
submitted in response to this RFA.  The NIAID and the NIAMS plan to
make approximately three and one awards, respectively in FY 1993,
contingent on the receipt of highly meritorious applications.  Funding
beyond the first and subsequent years of the grant will be contingent
upon satisfactory progress during the preceding years and the
availability of funds.

RESEARCH OBJECTIVES

Background

Silicone-containing implants and silicone injections have been linked
to the development of autoimmune-like diseases, such as scleroderma,
arthritis, and dermatomyositis, in some patients.  However, there are
no solid scientific data to support or rule out the link between the
onset of autoimmune disease and the presence of silicone in intact or
leaky implants.  Furthermore, very limited information is available
regarding the effects of silicone administration on the development of
normal immune responses and the maintenance of self-tolerance.  From
the available preliminary information, it appears that some silicone
polymers (e.g., D4) have biological activity in vivo similar to
Freund's complete adjuvant.  Basic research on the effects of silicone
in the immune system will be valuable in determining the safety of
these devices.

Research Goals and Scope

Some examples of relevant research topics include, but are not limited
to:

o  Effects of short- and long-term administration of silicone on the
production, structure, and function of lymphocytes

o  Effects of intracellular accumulation of silicone and low molecular
weight derivatives in macrophage function, including antigen processing
and presentation, cytokine production, and cytotoxic activities

o  Characterization of the profiles and fine specificity of
autoantibodies obtained from the sera of patients developing
autoimmune-like syndromes who have also received implants

o  Evaluation of the effects of silicone on lymphocyte and monocyte
interactions with endothelial cells and fibroblasts and the production
and function of adhesion molecules

o  Analysis of silicone effects on the evolution of autoimmune disease
in experimental systems, with regard to disease induction, course, and
immunologic parameters.

STUDY POPULATIONS

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

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 should be 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
compelling rationale should 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 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, NIH
recognizes that it may not be feasible or appropriate in all research
projects to include representation of the full array of U.S.
racial/ethnic minority populations (i.e., Native Americans, including
American Indians or Alaskan Natives, Asian/Pacific Islanders, Blacks,
and 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, diagnosis, or treatment of diseases, disorders or
conditions, including but not limited to clinical trials.

The usual NIH policies concerning research on human subjects also
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 to include 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 U.S. 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 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

Prospective applicants are asked to submit by September 15, 1992, a
letter of intent that includes a descriptive title of the overall
proposed research, the name and institution of the Principal
Investigator, and a list of the names of key investigators and their
institution(s).  The letter of intent is requested in order to provide
an indication of the number and scope of applications to be reviewed to
allow early preparations for review.  The letter of intent is not
binding and does not commit the sender to submit an application, nor is
it a requirement for submission of an application.  The letter of
intent is to be directed to:

Susana A. Serrate-Sztein, M.D.
Chief, Autoimmunity Section
Clinical Immunology Branch
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4A20
Bethesda, MD  20892
Telephone:  (301) 496-7985

APPLICATION PROCEDURES

Applications are to be submitted on the research grant application form
PHS 398 (rev. 9/91).  For purposes of identification and processing,
the box "Yes" should be marked in item 2a on the face page of the
application; the RFA number and the words "The Effects of Silicone on
the Immune Response" must be entered.

These application forms are available in most institutional business
offices and may be obtained from the Office of Grants Inquiries,
Division of Research Grants, National Institutes of Health, 5333
Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301)
496-7441.

The receipt date for applications is November 20, 1992.  Applications
that are not received by November 20, 1992, or that do not conform to
the instructions contained in the PHS 398 (rev. 9/91) application kit,
will be returned to the applicant without review.

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

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

In addition, mail two exact copies of the application directly to Dr.
Serrate-Sztein at the address given above under LETTER OF INTENT.

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 the application such that it may not reach the
review committee in time for review.

Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research Resources
may wish to identify the GCRC as a resource for conducting the proposed
research.  If so, a letter of agreement from either the GCRC program
director or Principal Investigator must be included with the
application.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed by the Division of Research
Grants (DRG) for completeness and by NIAID and NIAMS staff for
responsiveness.  Applications for the FIRST Award (R29) must include at
least three sealed letters of reference attached to the face page of
the original application.  FIRST Award (R29) applications submitted
without the required number of reference letters will be considered
incomplete and returned without review.  Those judged to be incomplete
and/or non-responsive will be returned to the applicant without review.
Applications will be reviewed for scientific and technical merit by an
appropriate scientific peer review group convened by the DRG, NIH.

The second level of review will be provided by the National Advisory
Allergy and Infectious Diseases Council or the National Arthritis and
Musculoskeletal Diseases Council in May 1993.

Applications in response to this solicitation will be reviewed by the
usual NIH peer review procedures.  The factors to be considered in the
evaluation of scientific merit of each application will be those used
in the review of unsolicited research project grant applications,
including the novelty, originality, and feasibility of the approach;
the training, experience, and research competence of the
investigator(s); the adequacy of the experimental design; the adequacy
and suitability of the facilities; the appropriateness of the requested
budget to the work proposed; and the adherence, whenever appropriate,
to NIH guidelines concerning adequate representation of minorities and
women in clinical research.

AWARD CRITERIA

The earliest anticipated date of award is July 1, 1993.  The following
will be considered in making funding decisions:  quality of the
proposed project as determined by peer review and availability of
funds.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.

Direct inquiries regarding programmatic issues to:

Susana Serrate-Sztein, M.D.
Chief, Autoimmunity Section
Clinical Immunology Branch
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4A20
Bethesda, MD  20892
Telephone:  (301) 496-7985
FAX:  (301) 402-2571

Dr. Michael D. Lockshin
Director, Extramural Programs
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Building 31, Room 4C32
Bethesda, MD  20892
Telephone:  (301) 496-0802

Direct inquiries regarding fiscal and administrative matters to:

Mr. Jeffrey Carow
Chief, Immunology Grants Management Section
Grants Management Branch
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4B29
Bethesda, MD  20892
Telephone:  (301) 496-7075

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance, No. 93.855 - Allergy, Immunology and Transplantation
Research and No. 93.846 - Arhtritis and Musculoskeletal and Skin
Diseases Research.  Grants are awarded under the authority of the
Public Health Service Act, Section 301 (42 USC 241) and administered
under PHS grants policies and Federal Regulations, most specifically at
42 CFR Part 52 and 45 CFR Part 74.  This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review.