kristoff@GENBANK.BIO.NET (Dave Kristofferson) (03/17/90)
NOTE: The NIH Guide may be split into more than one mail message to
avoid truncation during e-mail distribution. The first message always
begins with the RFP/RFA summary sections followed by the appended
texts of the full RFP/RFAs.
----------------------------------------------------------------------
NIH GUIDE - Vol. 19, No. 11, March 16, 1990
NOTICES
AVAILABILITY OF FISH OIL TEST MATERIALS ...................(84/205).......... 1
National Institutes of Health
Index: NATIONAL INSTITUTES OF HEALTH
PROMOTION OF INTEGRITY AND RESPONSIBLE PRACTICE IN BIOMEDICAL
RESEARCH - AAMC/NIH REGIONAL WORKSHOPS ....................(208/251)......... 2
National Institutes of Health
Index: NATIONAL INSTITUTES OF HEALTH
HEALTH AND SAFETY GUIDELINES FOR GRANTEES AND CONTRACTORS ..(254/357)........ 3
National Institutes of Health
Alcohol, Drug Abuse, and Mental Health Administration
Index: NATIONAL INSTITUTES OF HEALTH
ALCOHOL, DRUG ABUSE, AND MENTAL HEALTH ADMINISTRATION
NOTICES OF AVAILABILITY (RFPs AND RFAs)
IN VITRO METHODS TO ASSESS HUMAN METABOLISM OF CHEMICAL XENOBIOTICS (RFP) ... 4
National Institute of Environmental Health Sciences (363/391)
Index: ENVIRONMENTAL HEALTH SCIENCES
NOTICE: DEVELOPMENT OF NONMAMMALIAN MODELS FOR BIOMEDICAL
RESEARCH (RFA RR-90-01) ....................................(401/429)........ 5
National Center for Research Resources
Index: RESEARCH RESOURCES
ADDENDUM: KIDNEY DISEASES OF DIABETES MELLITUS: PATHOPHYSIOLOGY,
CLINICAL FEATURES, AND EPIDEMIOLOGY (RFA 90-DK-06) .........(432/457)........ 5
National Institute of Diabetes and Digestive and Kidney Diseases
Index: DIABETES, DIGESTIVE DISEASES, KIDNEY DISEASES
MENTAL RETARDATION RESEARCH CENTERS (RFA HD-90-07) ....(460/631, 884/1281)... 5
National Institute of Child Health and Human Development
Index: CHILD HEALTH, HUMAN DEVELOPMENT
HEALTH AND RETIREMENT STUDY (RFA 90-AG-02) ............(641/734, 1284/1688).. 8
National Institute on Aging
Index: AGING
COST-EFFECTIVE STRATEGIES OF CHOLESTEROL-LOWERING (RFA 90-HL-5-H) ........... 9
National Heart, Lung, and Blood Institute (737/780, 1691/2174)
Index: HEART, LUNG, BLOOD
INVOLVEMENT OF GROWTH REGULATING FACTORS IN SEX STEROID HORMONE ACTION
ON THE FEMALE GENITAL TRACT (RFA 90-HD-09) ............(783/866, 2177/2438).. 9
National Institute of Child Health and Human Development
Index: CHILD HEALTH, HUMAN DEVELOPMENT
NOTICES
AVAILABILITY OF FISH OIL TEST MATERIALS
P.T. 34; K.W. 0780000, 0780017
National Institutes of Health
This notice supplements the previous announcement published in the NIH Guide
for Grants and Contracts on August 25, 1989 (Vol. 18, No. 29).
SUMMARY AND PURPOSE
Additional Test Materials Currently Available
o EPA ethyl ester, prepared from menhaden oil, packaged in 1-5 gm portions
o DHA ethyl ester, prepared from menhaden oil, packaged in 1-5 gm portions
Processing and Specifications of Biomedical Test Materials
o EPA Ethyl Ester
The ethyl ester of EPA is prepared from vacuum-deodorized menhaden oil using
transesterification, urea adduction and short-path distillation to yield an
n-3 ethyl ester concentrate. The purified ethyl ester of EPA is attained by
supercritical fluid CO2 extraction from the n-3 ethyl ester concentrate
followed by high performance liquid chromatography. The product contains >95%
ethyl esters; of the ethyl esters EPA is 97%, other n-3's are <1%, n-6's are
<1% and other fatty acids are <1%.
~ DHA Ethyl Ester
The ethyl ester of DHA is prepared from vacuum-deodorized menhaden oil using
transesterfication, urea adduction and short-path distillation to yield an n-3
ethyl ester concentrate. The purified ethyl ester of DHA is attained by
supercritical fluid CO2 extraction from the n-3 ethyl ester concentrate
followed by high performance liquid chromatography. The product contains >95%
ethyl esters; of the ethyl esters DHA is 96%, other n-3's are <2%, n-6's are
<1% and other fatty acids are <1%.
FISH OIL TEST MATERIALS PROGRAM
The Fish Oil Test Materials Program is administered by the Division of
Nutrition Research Coordination in the Office of Disease Prevention, NIH. The
program was established in 1986 through the cooperation of the National
Institutes of Health (NIH), the Alcohol, Drug Abuse, and Mental Health
Administration (ADAMHA), and the National Oceanic and Atmospheric
Administration/Department of Commerce (NOAA/DOC). This program has been
designed to provide a long-term, consistent supply of
quality-assured/quality-controlled test materials to researchers in order to
facilitate the evaluation of the role that omega-3 fatty acids play in health
and disease.
Fish Oil Test Materials Advisory Committee
A Fish Oil Test Materials Advisory Committee (FOTMAC) is cochaired by
scientific staff from ADAMHA and NIH and is composed of scientists
representing the funding agencies (NIH, ADAMHA), the research community,
Department of Commerce (DOC) and the Food and Drug Administration (FDA). The
FOTMAC provides scientific advice to the DOC regarding the types of materials
needed by research scientists, shipping procedures for the materials, and
additional quality control and production issues. The committee is advisory
to the Fish Oil Test Materials Program on general programmatic issues such as
future directions and has produced a manual on Good Laboratory Practices for
the handling of polyunsaturated materials. In addition, the committee
provided guidance to DOC during the production of the Drug Master File
submitted to the FDA by the FOTMAC. Manuals on Analytical Methods for the
Quality Assurance of Fish Oil, Production Methods/Safety and Distribution were
produced by the DOC.
Fish Oil Test Materials Distribution Committee
A Fish Oil Test Materials Distribution Committee (FOTMDC) is composed of NIH
and other Federal scientists that do not use these products. The Distribution
committee processes the applications received from investigators, advises the
DOC of applicants that have fulfilled the application process, and makes
recommendations regarding the distribution of requested materials.
NIH GUIDE - Vol. 19, No. 11, March 16, 1990 - Page 1
APPLICATION PROCESS
To qualify to receive materials described in this announcement the applicant
must: 1) have peer-reviewed research indicating the need for the requested
materials, and 2) submit a correctly completed application form and a signed
waiver of liability. The committee will not be responsible for assessing the
scientific merit of the application. Regulations on human subjects and animal
research apply. In accordance with federal regulations, an IND number will be
required for the use of these materials in human studies. The FOTMAC has
established a drug master file at the FDA which includes manufacturing,
chemical composition and toxicological data relevant to these products.
Investigators using NOAA/DOC materials may reference this file in order to
expedite their IND requests. Availability of materials are contingent on
DOC/NOAA production capabilities. When prioritization is necessary, the order
will be: 1) NIH/ADAMHA funded, 2) other U.S. government funded, 3)
peer-reviewed, other funded, 4) NIH/ADAMHA approved, not funded, and 5) other.
The awarded materials are provided to investigators free of charge. Requests
for materials of amounts greater than 175 g/year of EPA ethyl ester and/or 100
g/year of DHA ethyl ester should not be submitted without prior discussion
with the NMFS - Charleston Laboratory. For further information contact Ms.
Patricia Fair at (803) 762-1200.
TEST MATERIALS AVAILABLE IN THE FUTURE
Test materials and their relevant application process will be announced in the
NIH Guide as new materials become available.
OTHER INFORMATION
Additional information will be provided to the investigator in the form of
complete quality assurance data for each lot of test material shipped,
stability data and storage instructions.
INQUIRIES AND APPLICATIONS
Investigators may obtain further information and apply for available fish oil
test materials for relevant studies by requesting an application form from:
Fish Oil Test Materials Program
Division of Nutrition Research Coordination
Building 31, Room 4B63
National Institutes of Health
Bethesda, MD 20892
Telephone: (301) 496-2323
PROMOTION OF INTEGRITY AND RESPONSIBLE PRACTICE IN BIOMEDICAL RESEARCH -
AAMC/NIH REGIONAL WORKSHOPS
P.T. 42; K.W. 1014004
National Institutes of Health
On April 20-21, the George Washington University will host the first of four
regional workshops sponsored by the Association of American Medical Colleges
(AAMC), under contract with the National Institutes of Health (NIH), to
address issues in the promotion of integrity and responsibility in biomedical
research. The regional workshops will serve as a forum for discussing recent
developments within the Public Health Service that include the establishment
of the Office of Scientific Integrity and the new regulation requiring awardee
institutions to assure that policies and procedures are in place for
investigating possible misconduct in science. The workshop will address
special topics such as training and mentoring, peer review and authorship
practices, and data ownership as well as dissemination of the information
developed by the Institute of Medicine study, "Promotion of Responsibility in
Research in the Health Sciences" supported by the NIH. The workshop is
expected to be of interest to program directors, investigators, and academic
administrators involved in behavioral and biomedical research. CME credits
will be available for the workshop through the George Washington University
Office of Continuing Medical Education.
Location: Holiday Inn Crowne Plaza, Arlington Virginia
NIH GUIDE - Vol. 19, No. 11, March 16, 1990 - Page 2
Contact:
Leah C. Valadez
The George Washington University Medical Center
Office of the Dean for Research
2300 Eye Street, N.W., Suite 514
Washington, DC 20037
Telephone: (202) 994-2801
Similar workshops are planned for Boston, Massachusetts; St. Louis, Missouri;
and San Diego, California. Dates will be announced in future notices.
HEALTH AND SAFETY GUIDELINES FOR GRANTEES AND CONTRACTORS
P.T. 34; K.W. 1014002, 0725010, 0725020
National Institutes of Health
Alcohol, Drug Abuse, and Mental Health Administration
This notice is a republication, with minor modifications, of an April 1989
issuance on this subject. It is being reissued to emphasize its continuing
importance.
Organizations receiving grant or contract awards are responsible for
protecting their personnel from hazardous conditions. The Government is not
legally liable for accidents, illnesses, or claims arising out of research
performed under its awards, but the National Institutes of Health (NIH) and
the Alcohol, Drug Abuse, and Mental Health Administration (ADAMHA) are
nonetheless aware that a variety of hazards threaten the safety and health of
both laboratory and clinical research personnel. Accordingly, the guidelines
that follow are designed to (1) identify potential hazards, (2) advise awardee
organizations and investigators of certain standards that should be considered
in order to address particular health and/or safety concerns, and (3)
emphasize that concerns about potentially hazardous conditions could result in
grant or contract funding delays until those concerns have been resolved to
the satisfaction of the awarding component.
1. Sources of potential danger to research personnel include the following
classes of hazard:
a. Biohazards (e.g., Human Immunodeficiency Virus, HIV; other
infectious agents; oncogenic viruses).
b. Chemical hazards (e.g., carcinogens; chemotherapeutic agents; other
toxic chemicals; flammable or explosive materials).
c. Radioactive materials.
2. The following guidelines and standards contain information designed to
assist grantees and contractors in providing a safe work environment for
research personnel. Therefore, depending upon the particular safety hazard at
issue, grantees and contractors are expected to consult these guidelines.
They may be obtained from:
Division of Safety
Office of Research Services
National Institutes of Health
Building, 31, Room 1C02
Bethesda, MD 20892
a. Biosafety in Microbiological and Biomedical Laboratories, U.S.
Department of Health and Human Services, Centers for Disease
Control and the National Institutes of Health. HHS Publication No.
(CDC) 88-8395.
b. Recommendations for Prevention of HIV Transmission in Health-Care
Settings. Morbidity and Mortality Report, August 21, 1987, Vol.
35, No. 2S.
c. Update: Universal Precautions for Prevention of Transmission of
Human Immunodeficiency Virus, Hepatitis B Virus, and Other
Bloodborne Pathogens in Health-Care Settings. Morbidity and
Mortality Weekly Report, June 24, 1988, Vol. 37, No. 24.
d. Recommendations for the Safe Handling of Parenteral Antineoplastic
Drugs, NIH Publication No. 83-2621.
NIH GUIDE - Vol. 19, No. 11, March 16, 1990 - Page 3
e. NIH Guidelines for the Laboratory Use of Chemical Carcinogens, NIH
Publication No. 81-2385.
The following materials are also recommended and may be purchased from:
National Academy Press
2102 Constitution Avenue, N.W.
Washington, D.C. 20418
A. Prudent Practices for Handling Hazardous Chemicals in the
Laboratory. Price $19.95
B. Prudent Practices for the Disposal of Chemicals from the
Laboratory. Price $19.95
C. Biosafety in the Laboratory: Prudent Practices for Handling and
Disposal of Infectious Materials. Price $29.95
3. Grant applications and contract proposals posing special hazards typically
are identified during the initial review process, but such concerns can
formally be expressed by agency staff or consultants at any time prior to
award. Regardless of the timing of the described concern, grant or contract
funding could be delayed until the matter has been resolved to the
satisfaction of the awarding component.
Special hazards that are identified after an award is made may lead to
suspension of work under the grant or contract pending corrective action by
the awardee. (See 45 CFR 74, Subpart M, concerning grant suspension and 48
CFR 12.5 concerning contract "stop work" orders.)
Grantee and contractor organizations are not required to submit documented
assurance of their specific attention to the guidelines and standards
identified in section 2 of this notice. However, where dictated by the
circumstances, grantees and contractors should be able to provide evidence
that pertinent health and safety standards have been considered and, where
necessary, have been put in practice. Such evidence may be requested by
appropriate NIH and ADAMHA staff; for example, during a site visit.
NOTICES OF AVAILABILITY (RFPs AND RFAs)
IN VITRO METHODS TO ASSESS HUMAN METABOLISM OF CHEMICAL XENOBIOTICS
RFP AVAILABLE: NIH-ES-90-06
P.T. 34; K.W. 0765020, 0755010
National Institute of Environmental Health Sciences
The National Institute of Environmental Health Sciences (NIEHS), National
Institutes of Health (NIH), is soliciting proposals for a project to compare
the in vitro metabolism of chemical xenobiotics in human tissue preparations
to similar preparations from animal species commonly used in laboratory
research and testing. Studies of hepatic metabolism shall be performed in
liver tissue slices. Metabolism in other tissues, or other tissue
preparations, if deemed necessary, shall be carried out using the best
available techniques. It is estimated that 3-4 chemicals per year shall be
studied. One contract is anticipated. The Request for Proposals (RFP) will
be released on or about March 21, 1990, with responses due by May 9, 1990.
All responsible sources may submit a proposal which shall be considered by the
Agency.
Requests should reference RFP NIH-ES-90-06 and should be forwarded to:
National Institute of Environmental Health Sciences
Contracts and Procurement Management Branch, OM
ATTN: Mary B. Armstead, Contracting Officer
79 T. W. Alexander Drive, 4401 Building
P.O. Box 12874
Research Triangle Park, NC 27709
NIH GUIDE - Vol. 19, No. 11, March 16, 1990 - Page 4
NOTICE: DEVELOPMENT OF NONMAMMALIAN MODELS FOR BIOMEDICAL RESEARCH
RFA: RR-90-01
P.T. 34; K.W. 0755020, 0780015, 0780020
National Center for Research Resources
The Division of Research Resources, now a part of the National Center for
Research Resources (NCRR), published a Request for Applications (RFA)
RR-90-01, Development of Nonmammalian Models for Biomedical Research, in the
NIH Guide for Grants and Contracts, Vol. 18, No. 44, December 15, 1989. A
modification has been made to the RFA.
Because of the shortened time for the review process, limited staff resources,
and the number of applications anticipated, applications may be subjected to a
triage by a peer-review group to determine their scientific merit relative to
the other applications received in response to this RFA. NIH will withdraw
from competition those applications judged to be noncompetitive and notify the
applicant and institutional business official. Those applications judged to
be competitive will be further evaluated for scientific/technical merit by
initial review groups which will be convened by the Office of Review, NCRR.
Those applicants who sent a letter of intent will receive this notice. If
further information is needed, please call:
Louise E. Ramm, Ph.D.
Biological Models and Materials Resources Program
National Center for Research Resources
Telephone: (301) 402-0630
ADDENDUM: KIDNEY DISEASES OF DIABETES MELLITUS: PATHOPHYSIOLOGY, CLINICAL
FEATURES, AND EPIDEMIOLOGY
RFA: 90-DK-06
P.T. 34; K.W. 0715075, 0765035, 0785035, 0785055
National Institute of Diabetes and Digestive and Kidney Diseases
Application Receipt Date: April 23, 1990
On January 19, 1990, the above mentioned Request for Applications (RFA) was
announced in the NIH Guide for Grants and Contracts, Vol. 19, No. 3. Because
the number of letters of intent received indicates that the number of
applications will be large compared to the number of awards to be made, the
NIH may conduct a preliminary scientific peer review to eliminate those
applications which are clearly not competitive. The NIH will administratively
withdraw from competition those applications judged to be noncompetitive and
will 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 in the RFA for
scientific and technical merit by an appropriate peer review group convened by
the Division of Extramural Activities, NIDDK.
All other aspects of the announcement remain the same.
MENTAL RETARDATION RESEARCH CENTERS
RFA AVAILABLE: HD-90-07
P.T. 04; K.W. 0715130, 0710030, 0745020, 0745027, 0745070
National Institute of Child Health and Human Development
Letter of Intent Receipt Date: April 16, 1990
Application Receipt Date: July 12, 1990
The National Institute of Child Health and Human Development (NICHD), through
the Mental Retardation and Developmental Disabilities (MRDD) Branch, Center
for Research for Mothers and Children (CRMC), invites research center core
grant applications (P30) to develop new knowledge in the field of prevention,
treatment, and amelioration of mental retardation and developmental
disabilities. Two centers may be supported in response to this announcement.
NIH GUIDE - Vol. 19, No. 11, March 16, 1990 - Page 5
The primary objective of the NICHD Mental Retardation Research Centers (MRRCs)
is to provide support and facilities for a cohesive, interdisciplinary program
of research and research training in mental retardation and related aspects of
human development.
NICHD has supported MRRCs through the provision of core grants (P30) which
facilitate program coordination and support central research core units.
Funds for the research projects using these core units come from independent
sources including Federal, State and private organizations. This announcement
seeks applications from existing MRRCs and from other comparable institutions
that meet the qualifications for a program of mental retardation research.
BACKGROUND
A major goal of the MRDD Branch's research program is to prevent and/or
ameliorate mental retardation. The degree of impairment associated with
mental retardation varies in relation to the cause. Moderate and more severe
mental retardation often results from problems that produce profound
alterations in brain development and/or function. Diminished intellectual and
adaptive capacity can often be traced to defective genes, teratogenic agents,
infections, nutritional deficits, accidents, diseases and other disorders
causing brain damage. A larger proportion of cases of mental retardation is
related to environmental conditions and disorders of unknown etiology. These
complex problems require integrated, multidisciplinary approaches involving
biomedical and/or behavioral sciences in a variety of settings.
The purpose of an MRRC is to provide a research environment in which
interdisciplinary collaboration among investigators who are working in areas
of relevance to the prevention and/or amelioration of mental retardation is
facilitated. Such research will cover a broad spectrum of scientific
approaches ranging from laboratory research on fundamental processes of
abnormal development to clinical and educational research in which persons
with mental retardation are studied.
It is thought that major solutions to the problems of mental retardation may
be found as a result of multidisciplinary collaboration involving a variety of
approaches in the MRRCs. As a result of the administrative and scientific
organization within a MRRC and across the network of MRRCs, opportunities for
breakthroughs will be enhanced.
RESEARCH SCOPE
MRRC Core Grants are intended to bring together in a center a variety of
disciplines to work on the common problems of mental retardation.
Consequently, applications for Mental Retardation Center Core Grants (P30)
should include investigators studying a range of topics in basic and clinical
or applied research. Applicants are encouraged, but are not required, to
include both biomedical and behavioral components from among the following
topics:
1. Developmental neurobiological studies relevant to MRDD.
2. Inborn errors of metabolism relevant to MRDD.
3. Genetic/cytogenetic disorders associated with MRDD.
4. Molecular biology; development of animal models.
5. Toxicology and physical environmental factors in the etiology,
treatment and prevention of MRDD.
6. Intellectual, behavioral, physical and the intergenerational effects
of malnutrition.
7. Developmental pharmacology and psychopharmacology.
8. Infectious diseases in the etiology, prevention and treatment of MRDD.
9. Diagnosis.
10. Perinatal problems associated with MRDD.
11. Psychobiological processes in MRDD.
12. Psychological processes in MRDD.
13. Early intervention for infants born at risk.
NIH GUIDE - Vol. 19, No. 11, March 16, 1990 - Page 6
14. Behavioral analysis of MRDD individuals.
15. Family and community studies.
16. Language and communication of MRDD populations.
17. Learning disabilities, dyslexia, and attention deficit disorder.
18. Behavior in residential and educational settings.
19. Socioecological processes.
20. Epidemiology of MRDD.
INCLUSION OF MINORITIES AND FEMALES IN STUDY POPULATION
PHS urges applicants to give added attention (where feasible and appropriate)
to the inclusion of minorities and women in study populations for research.
If minorities and women are not included, a clear rationale for their
exclusion should be provided. Investigators are reminded that merely
including arbitrary numbers of women and minority participants is a given
study is insufficient to guarantee generalizability of results.
ELIGIBILITY
Any of the following organizations are eligible to apply: Non-profit
organizations and institutions; State and local governments and their
agencies; and authorized Federal institutions.
MECHANISM, SCOPE AND SCALE OF SUPPORT
MRRC grants will be supported through the center core grant (P30) mechanism.
Review of applications and management of grants will be subject to applicable
policies for NIH research center grants.
Awards will be made for a period of five years. To be eligible for award as
an MRRC, the Center must provide core support for a minimum of 10 projects
funded from non-university sources.
The total direct costs requested for the first year may not exceed $500,000
for new grants and not more than 104% of the level recommended for the
previous budget period of a competing renewal grant. Budgets of applications
for new and renewal support will be stringently reviewed within these
guidelines. Applications with budget requests exceeding these guidelines will
be administratively withdrawn by NICHD and returned to the applicant.
ESTIMATED NUMBER OF AWARDS
This is the fourth of a series of annual announcements. Plans are to make two
awards in fiscal year 1991.
WHERE COMPLETE RFA MAY BE OBTAINED
A complete Request for Applications entitled "Mental Retardation Research
Centers (P30)" and guidelines concerning "NICHD Research Centers
Programs-Center Core Grants (P30)" may be obtained from:
Mental Retardation and Developmental Disabilities Branch
Center for Research for Mothers and Children, NICHD
Executive Plaza North, Rm. 631
6130 Executive Boulevard
Bethesda, MD 20892
Telephone: (301) 496-1383
This program is described in the Catalog of Federal Domestic Assistance No.
l3.865 Research for Mothers and Children. Awards will be made under the
authority of the Public Health Service Act, Section 30l (42 USC241) and
administered under PHS grant policies and Federal Regulations 42 CFR Part 52
and 45 CFR Part 74. This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or a Health Systems Agency
Review.
NIH GUIDE - Vol. 19, No. 11, March 16, 1990 - Page 7
HEALTH AND RETIREMENT STUDY
RFA AVAILABLE: 90-AG-02
P.T. 34; K.W. 0710010, 0730010, 0408006, 0404021, 0755018
National Institute on Aging
Letter of Intent Date: April 10, 1990
Application Receipt Date: May 23, 1990
The National Institute on Aging (NIA) invites applications for a cooperative
agreement to design and conduct a national longitudinal study of men and women
that focuses on the retirement process with emphasis on health issues. The
general objective of the study is to increase understanding of the
determinants and consequences of retirement in relation to health, economic
and psychosocial processes and outcomes.
Research is needed to answer numerous questions about the determinants and
dynamics of current retirement processes. For example, what objective health
problems and subjective perceptions of health make continued work difficult,
and what changes in the workplace could lessen these difficulties? What
pension incentives and penalties (in conjunction with individual financial
status and preferences) affect the timing of retirement, and what are the
relevant effects of the different types of private pensions, employer-provided
health benefits and the Social Security system? How has increased
participation of women in the labor force affected retirement decisions, and
to what extent are retirement decisions based on family rather than individual
considerations?
The proposed study should have the following general characteristics: a focus
on health and retirement; a longitudinal design with a national sample and a
household focus; linkages to administrative records such as employer health
and pension benefit records, Social Security earnings records, Medicare
records, and the National Death Index; and an emphasis on data quality.
The NIH urges applicants to include women and minorities in study populations.
If minorities and women are not included, a clear rationale for their
exclusion should be provided. Applicants funded under this Request for
Applications (RFA) will be supported through the Cooperative Agreement
assistance mechanism (UO1). An assistance relationship will exist between NIA
and the awardee to accomplish this activity. The award recipients define the
aims of the study and have the primary responsibility for the development and
performance of the activity. However, there will be government involvement in
a number of areas. These areas include the exploration of the use of
alternative sampling frames, the development of record linkages with
administrative files maintained by other federal agencies, and the
coordination of the study with other surveys of the older population in order
to enhance the capacity for comparative analyses.
Applications should include a suitable representation of women and minority
populations of individuals. Any variances from this should include a
reasonable explanation.
This RFA solicitation represents a single competition with a specified
deadline of May 23, 1990, for receipt of applications. Responsive
applications may be subjected to triage immediately preceding or concurrent
with evaluation by a peer review group to determine their scientific merit
relative to the other applications received in response to this RFA. NIH will
remove from consideration those applications judged to be noncompetitive.
Applications judged to be competitive will be fully reviewed for scientific
and technical merit by the same review group convened for this purpose by the
Scientific Review Office, NIA.
AVAILABILITY OF FUNDS
NIA has set aside $500,000 for the first year of the study. In the initial
application, support should be requested for five years. A competitive
continuation application may be submitted at a later date, but no funds have
been specifically reserved for renewals at this time. It is anticipated that
a single application will be funded.
Applications should be submitted on the Standard PHS Form 398 (10/88
revision). Separate instructions for completing Form 398 for this RFA are
available from the NIA official named below. These instructions provide
additional guidance in such areas as consortium arrangements, budget
preparation, etc. Complete line 2 of the application face page by typing in
"HEALTH AND RETIREMENT STUDY, RFA 90-AG-02." The RFA label (found in the
NIH GUIDE - Vol. 19, No. 11, March 16, 1990 - Page 8
application kit) 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 might not reach the review committee in time for review.
For a copy of the complete RFA and special instructions for filling out PHS
398, please contact:
Dr. Richard Suzman
Chief, Demography and Population Epidemiology
Behavioral and Social Research Program
National Institute on Aging
Building 31, Room 5C32
Bethesda, MD 20892
Telephone: (301) 496-3136
COST-EFFECTIVE STRATEGIES OF CHOLESTEROL-LOWERING
RFA AVAILABLE: 90-HL-5-H
P.T. 34; K.W. 0715035, 0705015, 0745027, 0408006, 0710095, 0755020
National Heart, Lung, and Blood Institute
Application Receipt Date: June 19, 1990
The Lipid Metabolism-Atherogenesis Branch of the Division of Heart and
Vascular Diseases, National Heart, Lung, and Blood Institute (NHLBI),
announces the availability of a Request for Applications (RFA) on the above
subject. Copies of the RFA are currently available from staff of the NHLBI.
This program will support the exploitation of existing data to develop
quantitative models of the potential health effects of cholesterol-lowering
and thereby to facilitate the evaluation of alternative strategies of
cholesterol-lowering. Such models might evaluate a variety of health outcomes
and compare the cost-effectiveness of cholesterol-lowering with other
modalities of prevention and treatment of coronary heart disease. A
multi-disciplinary approach, drawing on expertise in such areas as preventive
medicine, lipid disorders, biostatistics and health economics, is encouraged.
It is hoped that these models may be useful to the National Cholesterol
Education Program in future deliberations on treatment of high blood
cholesterol.
The support mechanism for this program will be the traditional, individual
research grant (RO1). Although approximately $300,000 for this program is
included in the financial plans for fiscal year 1991, award of grants pursuant
to this RFA is contingent upon receipt of funds for this purpose. It is
anticipated that two to four grants will be awarded under this program. The
specific amount to be funded, however, will depend on the merit and scope of
the applications received and the availability of funds.
Requests for copies of this RFA should be addressed to:
David J. Gordon, M.D., Ph.D.
Project Officer
Lipid Metabolism-Atherogenesis Branch
National Heart, Lung, and Blood Institute
Federal Building, Room 404
7550 Wisconsin Avenue
Bethesda, MD 20892
INVOLVEMENT OF GROWTH REGULATING FACTORS IN SEX STEROID HORMONE ACTION ON THE
FEMALE GENITAL TRACT
RFA AVAILABLE: 90-HD-09
P.T. 34; K.W. 0760020, 0760025, 0413002
National Institute of Child Health and Human Development
Application Receipt Date: June 15, 1990
The Reproductive Sciences Branch (RSB), Center for Population Research (CPR),
National Institute of Child Health and Human Development (NICHD), supports
research on human reproduction which relies on a variety of approaches in
biomedical sciences. Recently, scientific interest has surged with respect to
the involvement of growth regulating factors (or growth factors, local
NIH GUIDE - Vol. 19, No. 11, March 16, 1990 - Page 9
mediators) in gonadal function, and new information has been forthcoming
concerning the modulating/mediating roles of a variety of growth regulating
factors in gonadotropin actions on gonadal cells. In contrast to such gonadal
studies, little attention has been paid to date to investigating the possible
involvement of growth regulating factors in modulating sex steroid hormone
actions on the female genital tract.
This Request for Applications (RFA) is specifically designed to provide small
grants (R03) to stimulate research aimed at elucidating the involvement of
growth regulating factors in the sex steroid hormone action on the female
genital tract. Research may be proposed which seeks:
o To determine the kind of growth regulating factors involved in the
sex steroid hormone action on the female genital tract, by
identifying, quantitating and localizing growth regulating factors
and/or their receptors in the female genital tract in various
physiological conditions.
o To determine the manner of involvement of growth regulating factors
in the sex steroid hormone action by investigating the cause-effect
relationship between the involved growth regulating factors and/or
their receptors and the specific functional event(s) in the female
genital tract under the influence of the hormone.
o To fill the existing gap between our understanding of the
physiological, endocrinological aspects of sex steroid hormone
action and that of the molecular biological aspect, by
investigating the relationship between the gene expression induced
by sex steroid hormones and growth regulating factors and their
receptors at the cellular level by cell biological approaches.
o To investigate how the synergistic and antagonistic actions (or up-
and down-regulations) of one hormone on another are expressed in
terms of growth regulating factors.
If clinical studies are proposed in response to this RFA, applicants are urged
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 outcome, 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.
This RFA aims at soliciting independent investigators to conduct pilot studies
in order to develop the projects for preparation for R01 applications; thus,
this award is not intended to be used to supplement ongoing funded projects.
Up to six small grant awards (RO3) may be made as a result of this
announcement.
For further information and a copy of the full RFA, contact:
Koji Yoshinaga, Ph.D.
Reproductive Sciences Branch
Center for Population Research
National Institute of Child Health and Human Development
Executive Plaza North, Room 603
Bethesda, MD 20892
Telephone: (301) 496-6515
This program is described in the Catalog of Federal Domestic Assistance No.
13.864, Population Research. Awards will be made under the authority of the
Public Health Service Act 301 (42 USC 241) and 441 (USC 289d) and administered
under PHS Grant Policies and Federal Regulations 42 CFR Part 52 and 45 CFR
Part 74. This program is not subject to A-95 or Health Systems Agency review.
NIH GUIDE - Vol. 19, No. 11, March 16, 1990 - Page 10
ADDENDUM: KIDNEY DISEASES OF DIABETES MELLITUS: PATHOPHYSIOLOGY, CLINICAL
FEATURES, AND EPIDEMIOLOGY
RFA: 90-DK-06
P.T. 34; K.W. 0715075, 0765035, 0785035, 0785055
National Institute of Diabetes and Digestive and Kidney Diseases
Application Receipt Date: April 23, 1990
On January 19, 1990, the above mentioned Request for Applications (RFA) was
announced in the NIH Guide for Grants and Contracts, Vol. 19, No. 3. Because
the number of letters of intent received indicates that the number of
applications will be large compared to the number of awards to be made, the
NIH may conduct a preliminary scientific peer review to eliminate those
applications which are clearly not competitive. The NIH will administratively
withdraw from competition those applications judged to be noncompetitive and
will 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 in the RFA for
scientific and technical merit by an appropriate peer review group convened by
the Division of Extramural Activities, NIDDK.
All other aspects of the announcement remain the same.
NOTICE: DEVELOPMENT OF NONMAMMALIAN MODELS FOR BIOMEDICAL RESEARCH
RFA: RR-90-01
P.T. 34; K.W. 0755020, 0780015, 0780020
National Center for Research Resources
The Division of Research Resources, now a part of the National Center for
Research Resources (NCRR), published a Request for Applications (RFA)
RR-90-01, Development of Nonmammalian Models for Biomedical Research, in the
NIH Guide for Grants and Contracts, Vol. 18, No. 44, December 15, 1989. A
modification has been made to the RFA.
Because of the shortened time for the review process, limited staff resources,
and the number of applications anticipated, applications may be subjected to a
triage by a peer-review group to determine their scientific merit relative to
the other applications received in response to this RFA. NIH will withdraw
from competition those applications judged to be noncompetitive and notify the
applicant and institutional business official. Those applications judged to
be competitive will be further evaluated for scientific/technical merit by
initial review groups which will be convened by the Office of Review, NCRR.
Those applicants who sent a letter of intent will receive this notice. If
further information is needed, please call:
Louise E. Ramm, Ph.D.
Biological Models and Materials Resources Program
National Center for Research Resources
Telephone: (301) 402-0630
AVAILABILITY OF REQUEST FOR RESEARCH GRANT APPLICATION
RFA: 90-HD-09
INVOLVEMENT OF GROWTH REGULATING FACTORS IN SEX STEROID
HORMONE ACTION ON THE FEMALE GENITAL TRACT
P.T. 34; K.W. 0760020, 0760025, 0413002
NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
Application Receipt Date: June 15, 1990
BACKGROUND
The Reproductive Sciences Branch (RSB), Center for
Population Research (CPR), National Institute of Child
Health and Human Development (NICHD) supports
research dealing with the biomedical basis of reproduction
and its application to patient care. Research aimed at
alleviating human infertility through investigations of the
female genital tract is one of the high priority areas of the
RSB. Recently, scientific interest has surged with respect
to the involvement of growth regulating factors (or growth
factors, local mediators) in gonadal function and new
information has been forthcoming concerning the modulating/
mediating roles of a variety of growth regulating factors in
gonadotropin actions on gonadal cells. In contrast to such
gonadal studies, little attention has been paid to date to
investigating the possible involvement of growth regulating
factors in modulating/mediating sex steroid hormone actions
on the female genital tract. One known example of such
effects is found in the rapid growth of uterine tissues in
response to estrogen where there is a parallel fluctuation
of the uterine EGF receptor amount and the circulating
estrogen level. Thus, it seems quite likely that either
EGF receptor gene expression may be regulated by estrogen or
that estrogen action on the uterus may be modulated/mediated
by EGF receptor gene expression.
The recent availability of reagents for the localization and
quantitation of growth regulating factors, their receptors
and their molecular biological machinery, now makes it
feasible and timely to carry out experiments in this
important research area. Therefore, this RFA addresses
a priority area of reproduction research which is currently
not adequately supported and in which rapid progress is
deemed necessary. It is expected that the findings from
such studies will provide new insights into the hormonal
mechanisms modulating genital tract functions and knowledge
that is clinically useful in designing new approaches to the
therapy of infertility.
The purpose of this RFA is to indicate that CPR is
encouraging investigators to conduct research aimed at
elucidating the involvement of growth regulating factors in
the sex steroid hormone action on the female genital tract.
Because little research has been carried out in this area,
it is expected, at first, that such studies might seek to
identify the kind of growth regulating factors that are
involved in the sex steroid hormone action on the female
genital tract. It would also be expected that such
investigations seek to gain an understanding of
physiological roles of growth regulating factors in function
of the tissues and organs of the female genital tract.
Pharmacological studies, per se, are only justified if
clearly relevant to normal physiology.
Examples of research areas that might be considered to be
of high relevance to the RSB are described below. These
areas are intended to be representative examples of topics
which can be considered responsive to this RFA. Research
may be proposed which seeks:
o To determine the kind of growth regulating factors
involved in the sex steroid hormone action on the
female genital tract, by identifying, quantitating and
localizing growth regulating factors and/or their
receptors in the female genital tract tissues during
the ovulatory cycle, in the early stages of pregnancy
up to and inclusive of blastocyst implantation, and/or
during pseudopregnancy in relation to the endogenous
sex steroid hormone and their receptor levels.
o To determine the manner of involvement of growth
regulating factors in the sex steroid hormone action
by investigating the cause-effect relationship between
the involved growth regulating factors and/or their
receptors and the specific functional event(s) of the
female genital tract under the influence of the hormone.
o To fill the existing gap between our understanding of
the physiological, endocrinological and morphological
aspects of sex steroid hormone action and that of the
molecular biological aspect, by investigating the
relationship between the gene expression induced by sex
steroid hormones and growth regulating factors and their
receptor at the cellular level by cell biological
approaches.
o To investigate how the synergistic and antagonistic
actions (or up- and down-regulations) of one hormone
on another hormone are expressed in terms of growth
regulating factors.
In general, the projects of interest would be those aiming
to elucidate the physiological functions of the female
genital tract in which sex steroid hormone actions are
modulated/mediated locally by growth regulating factors in
terms of paracrine and/or autocrine mechanisms.
MECHANISMS OF SUPPORT
Applications in response to this RFA will compete for
funding in accord with the NIH small grants (R03) Program
as defined in this RFA and extant policies guiding the
research grant program of the NICHD. The receipt date for
this single competition RFA is June 15, 1990. It is
anticipated that up to six (6) grants will be awarded under
this program. The earliest start date for grant awards
would be April 1, 1991. Competitive awards will be made
contingent upon a sufficiently high level of merit and the
availability of funds.
I. PURPOSE OF THE AWARD
The purpose of this award is to facilitate support of pilot
projects testing new techniques or innovative/high-risk
projects which could provide a basis for more extended
research efforts. It is not the purpose of this award to
supplement any ongoing research efforts supported under an
existing Federal or non-Federal research grant. As this is
a small grant award, the budget may not exceed $50,000 per
year including indirect costs.
Funds may be requested for up to two (2) years. The award
is a non-renewable one- or two-year award. Personnel costs
should be limited not to exceed $20,000 per year.
II. ELIGIBILITY
Independent investigators with established, funded research
programs are eligible to apply for a Small Grant to support
research related to a topic described above. Submission of
an application under this announcement precludes concurrent
submission of a regular research grant application
containing the same research proposal. In addition, Small
Grant research support may not be used to supplement ongoing
research projects currently supported by Federal or non-
Federal funds, or to provide interim support of projects
under review by the Public Health Service.
III. APPLICATION REVIEW: PROCEDURES AND CRITERIA
Procedure
Applications will be reviewed by NIH staff for
responsiveness to the RFA. Nonresponsive applications will
be returned to the applicant unreviewed. If an application
is returned, the applicant then has the option to
appropriately revise it to suit the guidelines for the
traditional individual research grants (R01) to the NIH and
submit it for the next review deadline in the same manner
as unsolicited grant applications for the next review
cycle. An application will be considered unresponsive to
this RFA if it is identical to one already submitted to the
NIH for review, unless the previous application is
withdrawn. Applications submitted in response to this RFA
will be reviewed for scientific merit by an initial review
group convened by the NICHD to review these applications.
Review Criteria
Criteria for evaluation by the initial review group will,
except for consonance with the goals of the RFA, be the
same as for other research grant proposals. They are as
follows: scientific merit, the significance of proposed
questions, research design, methodology, data analysis
and interpretation; research experience and competence of
the applicant(s); adequacy of time and effort dedicated to
the project by investigators and staff; adequacy of
collaborative relationships, if applicable; adequacy of
existing and proposed facilities and resources; and costs
in relation to scope of the project.
METHOD OF APPLYING
Research grant applications should be made on Form PHS 398 (rev.
10/88). It is critical that Item 2 of the face page be marked
"In Response to Small Grant RFA-90-HD-09." In addition, the RFA
label available in the Form 398 must be affixed to the bottom of
the face page and placed on top of your entire package. Failure
to mark Item 2 on the face page and use the RFA label could
result in a delayed processing of your application such that it
may not reach the review committee in time for review. NIH Form
398 is available in most institutional business offices or from
the Division of Research Grants, NIH. In filling out the
application form, request no more than two (2) years in Item 6.
The budget page (page 4) should only request personnel up to
$20,000 per year, reasonable supplies and travel, small equipment
up to $2,000 per year, and minor "other" expenses. There is a
total cost limit of $50,000 per year.
Inclusion of Minorities in Study Population
If clinical studies are proposed in response to this RFA,
applicants are urged 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 outcome,
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.
The original and four (4) copies of the completed
application should be received by the Division of Research
Grants no later than June 15, 1990. Applications should
be directed to:
Application Receipt Office
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, Maryland 20892**
In addition to those applications mailed to the Division
of Research Grants, it is very important that two (2)
copies of the application be directed to:
Laurance Johnston, Ph.D.
Scientific Review Program
National Institute of Child Health
and Human Development
National Institutes of Health
6130 Executive Boulevard
Executive Plaza North, Suite 520
Bethesda, Maryland 20892
Late applications will not be accepted and will be
returned to the applicants.
For further information contact:
Koji Yoshinaga, Ph.D.
Reproductive Sciences Branch
Center for Population Research
National Institute of Child Health
and Human Development
National Institutes of Health
Executive Plaza North, Suite 603
Bethesda, Maryland 20892
Telephone: (301) 496-6515
This program is described in the Catalog of Federal Domestic
Assistance No. 13.864, Population Research. Awards will be
made under the authority of the Public Health Service Act
301 (42 USC 241) and 441 (USC 289d) and administered under
PHS Grant Policies and Federal Regulations 42 CFR Part 52
and 45 CFR Part 74. This program is not subject to A-95 or
Health Systems Agency review.
REQUEST FOR RESEARCH CENTER CORE GRANT APPLICATIONS
RFA: HD-90-07
P.T. 04; K.W. 0715130, 0710030, 0745020, 0745027, 0745070
MENTAL RETARDATION RESEARCH CENTERS
National Institute of Child Health and Human Development
Letter of Intent Receipt Date: April 16, 1990
Application Receipt Date: July 12, 1990
I. INTRODUCTION
The National Institute of Child Health and Human Development
(NICHD), through the Mental Retardation and Developmental
Disabilities (MRDD) Branch, Center for Research for Mothers and
Children (CRMC), invites research center core grant applications
(P30) as part of the Institute's Mental Retardation Research
Program to develop new knowledge in the field of diagnosis,
prevention, treatment, and amelioration of mental retardation and
developmental disabilities. Two centers may be supported in
response to this announcement.
A Mental Retardation Research Center (MRRC) is a center to
facilitate, through organization and operation, a program of
biomedical and/or behavioral research related to mental
retardation. MRRC core grants support multidisciplinary research
in areas which may lead to diagnosis, prevention, treatment,
and/or amelioration of mental retardation and developmental
disabilities. These grants fund core support services,
administration, and development of a limited number of new
research programs.
The primary objective of the NICHD Mental Retardation Research
Centers Program is to provide support and facilities for a
cohesive, interdisciplinary program of research and research
training in mental retardation and related aspects of human
development. Public Law 88-164, Title I, Part A authorized
construction of mental retardation research centers. NICHD has
provided partial support for a limited number of these centers
through the provision of core grants (P30) which facilitate
program coordination and support central research facilities.
Funds for the research projects using these core facilities come
from independent sources including Federal, State and private
organizations. This announcement seeks applications not only
from these constructed centers but also from other comparable
institutions that meet the qualifications for a program of mental
retardation research.
II. BACKGROUND
A major goal of the MRDD Branch's Mental Retardation Research
Centers Program is to prevent and/or ameliorate mental
retardation. The degree of impairment associated with mental
retardation varies in relation to the cause. Moderate and more
severe mental retardation often results from problems that
produce profound alterations in brain development and/or
function. Diminished intellectual and adaptive capacity can
often be traced to defective genes, teratogenic agents, toxic
substances, infections, nutritional deficits, accidents, diseases
and other disorders causing brain damage. A larger proportion of
cases of mental retardation is related to environmental
conditions and disorders of unknown etiology. These complex
problems require integrated, multidisciplinary approaches
involving biomedical and behavioral sciences in a variety of
settings.
More than 400 mental retardation syndromes have been identified,
and new ones are being discovered. Each requires fundamental
research into the underlying processes, as well as studies
designed to meet the unique needs of the afflicted children.
Therefore, one of the missions of the MRDD Branch is to support
research on the etiology, pathophysiology, epidemiology,
diagnosis and evaluation, prevention or amelioration of mental
retardation.
The purpose of an MRRC is to provide a research environment in
which interdisciplinary collaboration among investigators who are
working in areas of relevance to the prevention and amelioration
of mental retardation is facilitated. Such research will cover a
broad spectrum of scientific approaches ranging from laboratory
research on fundamental processes of normal and abnormal
development to clinical and behavioral research in which persons
with mental retardation are studied. It is thought that major
solutions to the problems of mental retardation may be found as a
result of multidisciplinary collaboration involving a variety of
approaches in the Mental Retardation Research Centers. As a
result of the administrative and scientific organization within a
MRRC and across the network of MRRCs, opportunities for
breakthroughs will be enhanced.
III. RESEARCH SCOPE
Mental Retardation Research Center Core Grants are intended to
bring together in a center scientists from a variety of
disciplines to work on the common problems of mental retardation.
Consequently, applications for Mental Retardation Center Core
Grants (P30) should include investigators studying a range of
topics in basic and clinical or applied research. Applicants are
encouraged, but are not required, to include both biomedical and
behavioral components among the topics addressed within their
center. Center grant applications must include among these
topics at least 5 of the following:
1. Developmental neurobiological studies relevant to MRDD:
neurophysiological, neuroanatomical, neurochemical,
neuropharmacological.
2. Inborn errors of metabolism relevant to MRDD:
pathophysiology, recombinant DNA technology, screening, applied
clinical and experimental studies, including treatment.
3. Genetic/cytogenetic disorders associated with MRDD:
antenatal diagnosis research on prevalent genetic causes of
mental retardation such as Down syndrome or Fragile X syndrome;
research on rare genetic disorders associated with mental
retardation.
4. Molecular biology: gene localization, structure, function
and organization; gene mapping; gene therapy; and development of
animal models.
5. Toxicology and physical environmental factors in the
etiology, treatment and prevention of MRDD; developmental and
behavioral teratology; subclinical levels of toxic agents and
their effects on morphological and behavioral changes associated
with mental retardation.
6. Effects of malnutrition (protein, calorie, micronutrients) on
intellectual, behavioral, social and physical development and the
intergenerational effects of malnutrition.
7. Developmental pharmacology and psychopharmacology:
medication used with MRDD populations.
8. Infectious diseases in the etiology, prevention and treatment
of MRDD; neurological, neuropathological, behavioral and
intellectual consequences of AIDS in children.
9. Diagnosis: development and application of biomedical and
behavioral methods and measures; identification of children and
infants at risk for MRDD.
10. Predictive and developmental studies of perinatal problems
associated with MRDD: developmental studies of low birth weight,
small for gestational age, preterm and neonatally sick infants.
11. Psychobiological processes in MRDD of conditions such as
autism and Rett syndrome using methods of behavioral genetics,
embryology and teratology, developmental neuroscience and
psychophysiology.
12. Psychological processes in MRDD: studies of cognitive and
information processing; attention and perception; sensory and
motor development; family, social and affective behavior; and,
motivation and personality.
13. Early interventions for infants born at risk: research into
the process of early intervention strategies.
14. Behavioral analyses: manipulations of interaction between
behavior and environments of individuals with MRDD to reduce
problem behaviors, facilitate vocational training, improve social
and self-help skills, and increase acquisition of adaptive
behaviors.
15. Family and community studies: parent-child and family
interactions; sexual behaviors; family structure and demographic
variables; family and community factors influencing developmental
outcomes and adjustment; community resources; caregiver behavior;
social support networks; and the effects of children with MRDD on
family life.
16. Language and communication of MRDD populations: studies on
development of alternative communication systems; ontogeny of
linguistic processes.
17. Learning disabilities, dyslexia, and attention deficit
disorder.
18. Residential and educational setting: effects on behavior
and adjustment of MRDD individuals; learning and social behavior
in educational settings; adaptation to residential environments;
aberrant behavior, e.g. self-injury.
19. Socioecological processes: interaction of MRDD individuals
in multiple settings (naturalistic observation); ethnographic
research; life history reporting; systematic observation of
specific activities.
20. Epidemiology of MRDD: analytic and case-control studies of
etiology; prevalence; follow-up of outcomes.
IV. INCLUSION OF MINORITIES AND FEMALES IN STUDY POPULATION
PHS urges applicants to give added attention (where feasible and
appropriate) to the inclusion of minorities and women in study
populations for research. If minorities and women are not
included, a clear rationale for their exclusion should be
provided. Investigators are reminded that merely including
arbitrary numbers of women and minority participants is a given
study is insufficient to guarantee generalizability of results.
V. MECHANISM, SCOPE AND SCALE OF SUPPORT
MRRC grants will be supported through the center core grant (P30)
mechanism. Review of applications and management of grants will
be subject to applicable policies for NIH research center grants.
Awards will be made for a period of 5 years. To be eligible for
award as an MRRC, the center must provide core support for a
minimum of 10 research projects funded from non-university
sources.
The total direct costs requested for the first year may not
exceed $500,000 for new grants nor more than 104% of the level
recommended for the previous budget period for a competing
renewal grant unless the latter is less than $500,000. Budget
increments for subsequent years generally will be limited to no
more than 4%. Budgets of applications for new and renewal
support will be stringently reviewed within these guidelines.
Applications with budget requests exceeding these guidelines will
be administratively withdrawn by NICHD and returned to the
applicant.
VI. METHOD OF APPLYING AND APPLICATION REQUIREMENTS
A Health Scientist Administrator in the MRDD Branch will advise
prospective applicants prior to submitting a proposal on
relevance of proposed concepts to the mission of the NICHD MRRC.
A. Guidelines
Detailed guidelines are found in "NICHD Research Centers
Programs-Center Core Grant (P30) Guidelines" (hereafter called
"NICHD Centers Guidelines"). This document may be obtained from:
MRDD Branch, CRMC
National Institute of Child Health
and Human Development
Room 631, Executive Plaza North
6130 Executive Boulevard
Bethesda, Maryland 20892
Telephone: (301) 496-1383
B. Eligibility
Any of the following organizations from the U.S. are eligible to
apply: nonprofit organizations and institutions; state and local
governments and their agencies; and authorized Federal
institutions.
C. Letter of Intent
If an investigator is satisfied that his/her institution meets
the qualifications prescribed and elects to apply for an MRRC
grant (P30), a letter of intent is requested (but not required)
to be submitted to the MRDD Program staff at the address given
above. The letter of intent should include a descriptive title,
should name the director and collaborators, and should identify
the core unit directors and principal investigators of the
research projects that would use the core unit services. It
should be submitted by April 16, 1990.
D. The Application
The applicant should submit the application using PHS 398
(revised 10/88). Application kits containing this form and the
necessary instructions are available in most institutional
business offices or may be obtained from the Division of Research
Grants, NIH. The NICHD recommends that the application be
developed in consultation with the MRDD Program staff, CRMC, who
will provide whatever guidance is possible and appropriate in
relation to both scientific and administrative issues.
Applicants for P30 MRRC grants must propose a program with a
theme relevant to the mission of the MRDD Branch as outlined
above. The program should consist of at least 10 externally
funded research projects grouped according to relevant topics.
These projects must be of high quality, providing a
multidisciplinary approach to the problem(s) being investigated.
Each project is to be summarized in accordance with the NICHD
Centers Guidelines.
The MRRC Director should be a scientist or science administrator
who can provide effective administrative and scientific
leadership. The Director will be responsible for the
organization and operation of the MRRC and for communication with
the NICHD on scientific and operational matters. Scientific
personnel and institutional resources capable of providing a
strong research base in the fields specified must be available.
In addition, the institution and pertinent departments have to
show a strong commitment to the center's support. Such
commitment may be provided as dedicated space, salary support for
investigators, dedicated equipment, or other financial support
for the proposed MRRC.
Each core unit proposed for funding under the MRRC grant must be
utilized by at least three federally funded research projects,
one of which is NIH funded, exclusive of research contracts,
interagency agreements, and NIH-supplemental projects funded by
other agencies. Subprojects within a program project (POl) will
be considered as individual projects comparable to an ROl. A
detailed description of each core unit proposed as part of the
center must be provided with detailed budget and budget
justification. A scientist must be named as responsible for each
core unit proposed. The description of the core units proposed
should include a rationale to show how they will support the
research effort in a cost effective manner. Facilities must be
available for the primary needs of the MRRC Program and require
no more than modest alteration and/or renovation. Funds for new
construction will not be provided.
Promoting interdisciplinary collaboration among scientists
working within a Center is a major goal of the MRRC Program.
Each MRRC applicant should submit a plan, as part of the
application, to assure continuing interaction among participating
scientists from different disciplines.
Another goal of the MRRC Program is to attract scientists to the
field of mental retardation research. Therefore, where
appropriate, the applicant may request "New Program Development"
funds for direct research support of one or more projects, not to
exceed a total of $50,000 per year or 10% of total direct cost,
whichever is less. Such funds might serve to attract new
investigators to the Center, to develop a new area or program of
research, or to facilitate the development of newly trained
investigators' research programs. New Program Development
proposals should be comparable to ROl research proposals. Each
such proposal can provide support for only two years for any one
investigator.
It is a major goal of the NICHD to promote active collaboration
among MRRCs. To accomplish this goal, the successful applicants
will be encouraged to participate in the collaborative efforts of
established MRRC programs. Some consideration should be given,
in planning the program, to potential collaborative studies and
projects that might be proposed for the MRRC network.
VlI. TIMETABLE FOR RECEIPT AND REVIEW OF APPLICATIONS
A. Receipt Date
This is the fourth of a series of annual announcements. Plans
are to make two awards in fiscal year 1991. The original and
four copies of the application are due in the Division of
Research Grants on or before July 12, 1990. NICHD will not
accept any applications in response to this announcement for new
grants with first year budget requests exceeding $500,000 in
direct costs. Applications must be sent to:
Application Receipt Office
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, Maryland 20892**
The RFA label contained in the application kit should be affixed
at the bottom of the face page of the application. Failure to
use this label could delay processing of the application and
delay assignment to the appropriate review committee.
Applications should be identified by checking the "yes" box in
Item Number 2 on the face page of the application and typing in
the words "In response to RFA-HD-90-07, Mental Retardation
Research Center Grant (P30)." Two copies of the application
should be sent to:
Director, Scientific Review Program
National Institute of Child Health
and Human Development
Executive Plaza North, Room 520
6130 Executive Boulevard
Bethesda, Maryland 20892
B. Review Schedule
Applications received in response to this RFA will be reviewed
together on a nationwide competitive basis. The initial review
for scientific merit will be carried out by the NICHD Mental
Retardation Research Committee (MRRC) at its March 1991 meeting.
Because a site visit is not a prerequisite for MRRC
consideration, each application should be thorough and complete
enough to stand on its own. The second-level review will be made
by the National Advisory Child Health and Human Development
Council at its June, 1991 meeting, for funding beginning August
1991.
This program is described in the Catalog of Federal Domestic
Assistance No. 13.865 Research for Mothers and Children. Awards
will be made under the authority of the Public Health Service
Act, Section 301 (42 USC241) and administered under PHS grant
policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part
74. This program is not subject to review by a Health Systems
Agency.
REQUEST FOR APPLICATIONS FOR COOPERATIVE AGREEMENT
HEALTH AND RETIREMENT STUDY
RFA: 90-AG-02
P.T. 34; K.W. 0710010, 0730010, 0408006, 0404021, 0755018
National Institute on Aging
Letter of Intent Due: April 16, 1990
Application Due: May 23, 1990
Award Announcement (Start Date): September 15, 1990
INTRODUCTION
Retirement and health policy issues are among the most
important issues that our society must address. With
greater longevity, a dramatic decrease in the average
retirement age, and a rapidly increasing older population,
policies that affect retirement behavior, the resources
available to older people, and the financial and health care
needs of older people have particular significance. The
aging of the population in the United States has broad
implications for both older Americans and for the population
as a whole. Our understanding of the determinants and the
short- and long-term consequences of contemporary retirement
patterns is seriously inadequate. The previous major study
on retirement paid too little attention to health issues,
and many findings from that study are obsolete. There is
currently no study that combines suitable data about the
labor force behavior, retirement, health, and economic
status of older people.
PURPOSE AND SCIENTIFIC BACKGROUND
This announcement invites applications for cooperative
agreements to design and conduct a national longitudinal
study of men and women which focuses on the retirement
process with emphasis on health issues. The general
objective of the study is to increase understanding of the
determinants and consequences of retirement in relation to
health, economic and psychosocial processes and outcomes.
Research is needed to answer numerous questions useful to
the scientific community about the determinants and dynamics
of current retirement processes. For example, what
objective health problems and subjective perceptions of
health make continued work difficult, and what changes in
the workplace could lessen these difficulties? What pension
incentives and penalties (in conjunction with individual
financial status and preferences) affect the timing of
retirement, and what are the relevant effects of the
different types of private pensions, employer-provided
health benefits and the Social Security system? How has
increased participation of women in the labor force affected
retirement decisions, and to what extent are retirement
decisions based on family rather than individual
considerations?
Similar illustrative questions can be posed about both the
short- and long-term consequences of specific retirement
patterns on health and functional status, financial
resources for the retirement years including health care and
possible long-term care needs, consumption patterns, the
financial status of older widows, mobility, etc.
Recent studies of retirement have not had adequate samples,
have not been longitudinal in design, and have not included
information in the same study (and for the requisite family
members) on labor market activities and transitions, pension
plans, financial status, health and functional status, and
psychosocial dimensions. Thus, while the determinants of
current retirement patterns, for example, are thought to be
multifactorial, it has not been possible to test a wide range of
competing hypotheses against each other.
Programmatic Background
In a May 1988 report to the National Institute on Aging (NIA) on
data collection priorities, an Ad Hoc Advisory Group to the NIA
Extramural Program strongly recommended that the NIA support a
new longitudinal survey that would address retirement and health
issues. The survey and concept were unanimously endorsed by the
National Advisory Council on Aging. Since then, the NIA has held
workshops relevant to this topic. The issue also was recognized
as an important priority in both the House and Senate
Appropriations Committees' FY1990 budget reports.
RESEARCH GOALS AND SCOPE OF THE PROJECT
The proposed study should have the following general
characteristics:
o Focus on Retirement and Health. The study should focus on
retirement issues, and on the relationships between
retirement and health.
o Longitudinal Design. Longitudinal data (including the
timing and sequencing of critical events) are essential in
understanding most of the scientific questions related to
health and retirement. Although applications are limited to
a maximum period of five years, study designs should include
the potential for a longer term study. The sample should
probably be reinterviewed at least every two years, and new
cohorts should be added periodically to enable the study of
trends over time.
o Household Focus. Many analytic issues require appropriate
information from both spouses in intact families.
o Linkages to Administrative Records. Many analytic issues
related to retirement need information that often cannot be
reliably supplied by respondents and require linkages to
administrative data such as employer health and pension
benefit records, Social Security earnings records, Medicare
records, and the National Death Index. Initial sample
membership must not preclude future microanalysis with
linked administrative files.
o Emphasis on Data Quality. There is a scientific need for
the highest quality of data. On balance, data quality is
probably a more important concern than other study
characteristics, such as sample size.
The study should include the following phases:
Phase 1 - Study design and preparation (approximately 12
months). Phase 2 - Data collection and dissemination for
baseline survey. Phase 3 - Data collection and dissemination
for at least one follow-up wave.
Applicants are encouraged to consider the need (beyond
analyses reporting initial findings) for small-scale
methodological and analytical studies that may lead, for
example, to improved collection of reliable labor force or
occupational histories and changes, efficient description of
benefit plan information, work capacity and workplace
demands and characteristics, or improved consistency across
waves, etc.
NIH urges applicants to include women and minorities in
study populations. If minorities and women are not
included, a clear rationale for their exclusion should be
provided.
Requested Budget and Budget Alternatives.
The application should include an adequately justified
budget for the entire project period of five years.
Estimates of personnel needs, including the Principal
Investigator, other investigators, and support staff should
be submitted. The budget should be expressed in both a
twelve-month period format and according to each phase.
Up to $500,000 in total costs (both direct and indirect)
will be allocated for the first year of the study. The
precise funding available for subsequent years is not yet
determined, though between $1.75 million and $2.25 million
in total direct and indirect costs are anticipated for each
subsequent year of the study. The final budget will be
negotiated based on the specific characteristics of the
study to be implemented. In the initial application,
support should be requested for five years. A competitive
continuation application may be submitted at a later date,
but no funds have been specifically reserved for competitive
continuations at this time. It is anticipated that a single
application will be funded.
TERMS OF AWARD
The study will be supported by the Cooperative Agreement
assistance mechanism (UO1) which is subject to the same
administrative requirements as grants. The regulations and
policies that govern the research grant programs of the PHS
(described in the PHS Grants and Policy Statement 1/1/87)
will prevail. The awarding of a cooperative agreement
pursuant to this Request for Applications (RFA) is
contingent on receipt of meritorious
applications. While the cooperative agreement is similar to
a traditional NIH research project grant, it differs in the
extent and the nature of involvement of NIA staff. In a
cooperative agreement, there is substantial programmatic
involvement of the designated NIA Program Administrator
above and beyond the levels characteristic for traditional
program management of grants.
Organizational Structure.
o Awardee. Under the terms of the cooperative agreement,
the awardee identifies the issues to be studied, defines the
design and details of the study within the guidelines of the
RFA, retains primary responsibility for performance of the
activity including analyzing and publishing results, and
maintains ownership over data collected. The awardee agrees
to accept assistance from the designated NIA Program
Administrator in aspects of the scientific and technical
management of the study according to the terms of this RFA.
o Steering Committee. The Steering Committee will serve as
the main advisory group to the Principal Investigator. The
Steering Committee will be chaired by the Principal
Investigator and will include the NIA Program Administrator
and a minimum of three members appointed by the Principal
Investigator. The primary function of the Steering
Committee will be to advise the Principal Investigator on
major policy decisions affecting the study. The Steering
Committee will meet approximately three times during the
first year of the study, and approximately twice a year for
the remaining years of the study. All Steering Committee
expenses should be budgeted for in the cooperative agreement
application (with the exception of expenses for the NIA
Program Administrator).
o Data and Design Monitoring Committee. The purpose of this
Committee is to monitor the study and advise the NIA Program
Administrator. The Committee and its chair will be
appointed by the NIA and will include the NIA Program
Administrator, and scientific experts in areas appropriate
to a national longitudinal survey on health and retirement
from the scientific community or other Federal Agencies.
The Principal Investigator will make presentations to, and
discuss the study with, this Committee. The NIA Program
Administrator will consider the recommendations of the
Committee in deciding how to advise the Principal
Investigator, and whether to approve each phase of the
study.
The Data and Design Monitoring Committee will meet
approximately three times during the first year and
approximately twice per year thereafter. Meetings will be
held in Bethesda, Maryland. Expenses for Committee members
representing the scientific community will be paid for by
the NIA; and, to avoid impact on the awardee, expenses for
members representing Federal Agencies will be paid for by
their respective agencies. Awardee expenses for these trips
should be budgeted for in the cooperative agreement
application.
o NIA Program Administrator. The Program Administrator will
approve each phase of the study before the awardee can
proceed to the subsequent phase. Prior approval is required
by the NIA Program Administrator for any replacements of key
personnel or other changes in subcontracts. The designated
NIA Program Administrator will assist in refining study
objectives, methodologies, and survey instruments,
initiating and maintaining collaborative relationships, and
analyzing and publishing the results of the study.
The NIA Program Administrator will assist the investigator
in exploring the use of alternative sampling frames, in
developing record linkages with administrative files
maintained by other federal agencies and in coordinating the
study with other surveys of the older population in order to
enhance the capacity for comparative analyses.
These special Terms of Award are in addition to, and not in
lieu of, otherwise applicable OMB administrative guidelines,
HHS grant administration regulations at 45 CFR Part 74, and
other HHS, PHS, and NIH grant administration policies. If
any decision made by the designated NIA Program
Administrator is unacceptable to the awardee, and a mutually
acceptable compromise cannot be reached, the awardee may,
within 30 days of receipt of the program decision, request a
review of the decision by an arbitration panel composed of
one nominee chosen by the awardee, one chosen by the
designated NIA Program Administrator, and one chosen by the
first two nominees. This panel will render a decision
within 60 days of the request. These special arbitration
procedures in no way affect the awardee's right to appeal an
adverse action in accordance with PHS regulations at 42 CFR
Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.
REVIEW PROCEDURES AND CRITERIA
Applications will be received by the NIH Division of
Research Grants and will be assigned to the NIA.
Applications judged by the NIA to be nonresponsive will be
returned. Responsive applications may be subjected to
triage immediately preceding or concurrent with evaluation,
by a peer review group to determine their scientific merit
relative to the other applications received in response to
this RFA. NIA will remove from consideration those
applications judged to be noncompetitive for award. Those
applications judged to be competitive will be fully reviewed
for scientific and technical merit by a review group
convened for this purpose by the Scientific Review Office,
NIA. The next stage of the review will be conducted by the
National Advisory Council on Aging.
In addition to the traditional R01 criteria for merit,
applications will be reviewed using the following criteria:
o Experience and Expertise. Experience and expertise will
be given heavy weight in the review. The study should be
conducted by an organization and team that has substantial
experience with multi-wave national longitudinal studies,
including study design and all relevant aspects of data
collection. In order to ensure that the collected data will
be appropriate for longitudinal analysis the design team
should include experience in the analysis of comparable
longitudinal data. The applicant team should have
substantial experience in research on the retirement process
as well as appropriate experience in economics, the
assessment of health and functional status, and relevant
social and behavioral factors.
o Sampling Frame. The application will be evaluated in
terms of the availability of an appropriate national
sampling frame that will permit appropriate linkage to
administrative records and analysis of linked micro-data.
o Analytic Issues and Study Design. The proposed studies
will be evaluated according to effective identification and
prioritization of the important research questions in
retirement and related health and economic factors and a
thoughtful consideration of the major study design issues in
terms of soundness, originality and appropriateness for
dynamic longitudinal analyses.
o Data Quality, File Construction and Dissemination of
Results. The scientific need is for the highest possible
quality of data. The applicant team and proposed study will
also be evaluated in terms of ability to collect high
quality data. The ability to efficiently construct high
quality longitudinal files from complex information on
multiple household members, and rapidly report the initial
results will also be evaluated.
METHOD OF APPLYING AND APPLICATION REQUIREMENTS
Organizations considering an application in response to this
RFA are strongly encouraged to discuss their application
with the NIA Program Administrator in advance of formal
submission. Prospective applicants are urged to submit a
brief letter of intent to the National Institute on Aging.
This letter should include the name of the Principal
Investigator and other key personnel, the name of the
applicant organization, and the names of any other key
organizations. This letter should be received no later than
April 16, 1990. Inquiries, and letters of intent should be
directed to the following NIA official:
Dr. Richard Suzman
Chief, Demography and Population Epidemiology
Behavioral and Social Research Program
National Institute on Aging
Building 31, Room 5C32
Bethesda, MD 20892
Telephone: (301) 496-3136
Applications should be submitted on the standard PHS Form
398 (October 1988 revision). These forms can be obtained
from most institutional business offices, or directly from
NIH:
Office of Grants Inquiries
Division of Research Grants
National Institutes of Health
Westwood Building, Room 449
Bethesda, MD 20892
Telephone: (301) 496-7441
The completed application, along with six copies of the
application and six copies of any appendices, should be
submitted by May 23, 1990.
Separate instructions for
completing Form 398 for this RFA are available from the
above-named NIA official. These instructions provide
additional information in such areas as consortium
arrangements, budget preparation, etc. Complete line 2 of
the application face page of the PHS 398 (rev. 10/88) by
typing in "HEALTH AND RETIREMENT STUDY, RFA 90-AG-02." The
RFA label (found in the 10/88 revision of 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 might not reach the review
committee in time for review. The completed application
materials and four (of the six) copies including four copies
of the appendices should be mailed to
the following address:
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD 20892**
The other two copies including two copies of the appendices
should be submitted directly to the
NIA at the following address:
Chief, Scientific Review Office
National Institute on Aging
Building 31, Room 5C12
Bethesda, MD 20892
The programs of the NIA are identified in the Catalogue of
Federal Domestic Assistance, number 13.866. Awards will be
made under the authority of the Public Health Service Act,
Title III, Section 301 (Public Law 78-410, as amended; 42
USC 241) and administered under PHS grant policies and
Federal regulations, most specifically 42 CFR Part 52 and 45
CFR Part 74. This program is not subject to the
intergovernmental review requirements of Executive Order
12372, or to Health Systems Agency Review.
REQUEST FOR RESEARCH GRANT APPLICATIONS: RFA NIH 90-HL-5-H
COST-EFFECTIVE STRATEGIES OF CHOLESTEROL-LOWERING
P.T. 34; K.W. 0715035, 0705015, 0745027, 0408006, 0710095, 0755020
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
Application Receipt Date: June 19, 1990
PURPOSE
The Division of Heart and Vascular Diseases, National Heart,
Lung, and Blood Institute (NHLBI), invites grant
applications to develop quantitative models of the potential
extension of life and good health attainable by lowering
blood cholesterol levels to prevent the progression and
sequelae of atherosclerotic coronary heart disease (CHD) and
to use these models to evaluate the potential overall health
effects and costs of alternative strategies of cholesterol-
lowering. Such models might incorporate a variety of health
outcomes and compare cholesterol-lowering with other
modalities of CHD prevention and treatment.
DISCIPLINES AND EXPERTISE
A multi-disciplinary approach, drawing on expertise in such
areas as preventive medicine, lipid disorders, behavioral
medicine, biostatistics and health economics, is encouraged.
Applicants might represent academic medical institutions,
state and local health organizations, or professional or
voluntary health organizations.
BACKGROUND
Since the 1984 publication of the results of the Lipid
Research Clinics Coronary Primary Prevention Trial,
cholesterol-lowering has been increasingly accepted by
physicians and patients as a means of preventing CHD events.
The 1984 NIH Consensus Conference identified one-quarter of
men and women above age 20 as candidates for dietary
intervention, with those in the top cholesterol decile as
potential candidates for cholesterol-lowering drugs. A 1986
NHLBI survey of physicians found that nearly 90% of
respondents agreed with these recommendations, though only
60% found them feasible in practice. Since 1987, the growing
acceptance of cholesterol-lowering as standard medical
practice has been enhanced by the following developments:
1 The 1987 release by the National Cholesterol Education
Program (NCEP) of its guidelines for detection, evaluation
and treatment of high blood cholesterol in adults. These
guidelines extended and refined the recommendations of the
1984 Consensus Panel and offered specific practical advice to
the physicians who will use them.
2 The FDA approval of lovastatin, the first of a powerful
new class of cholesterol-lowering drugs, the HMG CoA
reductase inhibitors, that produce a mean 40% reduction in
low-density lipoprotein (LDL) cholesterol in dosages that are
well tolerated by nearly all patients. Two similar drugs,
pravastatin and simvastatin, are currently under development.
3 The publication of the results of the Helsinki Heart Study
(HHS), which showed a significant reduction in CHD morbidity
and mortality in men receiving gemfibrozil, as compared with
those receiving a placebo. This study was noteworthy in that
increases in high-density lipoprotein (HDL) cholesterol as
well as the (modest) decreases in LDL cholesterol appeared to
contribute to the favorable result.
4 Results of angiographic studies such as the Cholesterol-
Lowering Atherosclerosis Study (CLAS) and the Familial
Atherosclerosis Treatment Study (FATS), which showed
significantly delayed progression (and regression in some
cases) of coronary atherosclerotic lesions in coronary
patients receiving regimens of colestipol, niacin or
lovastatin, and diet in as little as two years. The marked
lipid changes produced by the experimental regimens in these
studies, including substantial increases in HDL cholesterol
in the niacin-containing regimens, and the demonstration of
significant treatment benefit in CLAS patients with baseline
cholesterol levels below 240 mg/dl at entry were also
noteworthy.
With the accumulation of clinical trial evidence confirming
the scientific validity of the cholesterol hypothesis,
increasing scrutiny has been directed toward the translation
of these results to health policy. Some investigators have
argued that even if the approximately 2% reduction in CHD
risk per 1% reduction in cholesterol predicted by
epidemiologic studies and clinical trials is valid and is not
offset by adverse effects on other causes of mortality, the
projected gain in life expectancy from established
cholesterol-lowering regimens is trivial for the patient
without other major CHD risk factors. Given the costs
involved in implementing large-scale cholesterol-lowering
efforts like that recommended by the NCEP and given the
modest efficacy of diet and of the first-line drugs
identified in the guidelines issued by its adult treatment
panel, the cost-effectiveness of such efforts relative to
that of other preventive and therapeutic measures competing
for the same health care resources has been questioned.
The quantification of costs and benefits of any widely-
implemented health policy is very complex and requires many
assumptions that are difficult to validate. Estimations of
changes in life expectancy that rely on extrapolation from
short-term epidemiologic follow-up data may underestimate the
potential long-term health benefits of cholesterol reduction,
because they emphasize the modest short-term predictive value
of cholesterol levels in the elderly for CHD events and
ignore the influence of cholesterol levels in youth and
middle age on the atherosclerotic burden and CHD risk of the
elderly. Published 30-year follow-up data from Framingham
suggest that mortality rates after age 65 (the age after
which nearly 80% of all CHD deaths occur) are most strongly
influenced by cholesterol levels below age 48. Also,
estimations of costs and benefits of cholesterol-lowering
strategies employed in artificial research settings (e.g.,
randomized clinical trials) may not accurately reflect their
implementation in a realistic clinical setting. Published
models have also tended to focus on mortality, without
considering the full range of potentially preventable health
consequences (and costs) of nonfatal CHD events or the
potential beneficial or adverse effects of cholesterol-
lowering on quality of life.
A broad and thorough exploration of the potential health
benefits and costs of cholesterol-lowering is needed. This
exploration might include identification and analysis of
epidemiologic data bases with long-term follow-up;
development and validation of methods for modeling long-
term follow-up with intermediate- or short-term data; and
expanding the scope to include postponement of illness and
disability as well as death. The cost-effectiveness of
alternative strategies of cholesterol-lowering might be
compared among each other as well as with other medical
interventions (treatment of hypertension, coronary bypass
surgery, etc.) aimed at reducing CHD morbidity and mortality.
It is anticipated that the 1987 NCEP guidelines would provide
the standard with which other strategies are compared. These
guidelines represented an attempt by an expert panel to
incorporate current scientific knowledge, although they
included compromises and a degree of arbitrariness in
ambiguous areas. Some elements of the NCEP guidelines in
which a plausible scientific case could be made for a more
conservative or a more aggressive approach are the use of
identical LDL cutpoints in all age groups, the scheme for
modifying these cutpoints in the presence of existing CHD
and/or other risk factors, the handling of sex differences,
and the limited role of high-density lipoprotein (HDL) in the
decision-tree. Even small changes in the decision-tree could
have a large impact on the numbers of people earmarked for
treatment and on the overall cost of implementing these
guidelines.
With advances in medical research and technology and the
development and increasing utilization of newer, more
effective drugs, the NCEP guidelines are likely to undergo
revision. The development of valid quantitative models for
the health effects of cholesterol-lowering will help future
expert panels weigh the beneficial effects against the costs
of alternative approaches and may thereby help provide a
rational basis for incorporating our evolving scientific
knowledge and technological capacity into cost-effective
strategies for CHD prevention in the future.
REFERENCES
1 Anderson KM, Castelli WP, Levy D. Cholesterol and
mortality: 30 years of follow-up from the Framingham Study.
JAMA 1987; 257:2176-2180.
2 Browner WS. Estimating the impact of risk factor
modification programs. Am J Epidemiol 1986; 123: 143-153.
3 Castelli WP, Garrison RJ, Wilson PWF, Abbott RD,
Kalousdian S, Kannel WB. Incidence of coronary heart disease
and lipoprotein cholesterol levels. JAMA 1986; 256:2835-
2828.
4 Cupples AL, D'Agostino RD: Some risk factors related to
the annual incidence of cardiovascular disease and death
using pooled repeated biennial measurements: Framingham
Heart Study, 30-year follow-up: Section 34. In Kannel WB,
Wolf PA, Garrison RJ (eds): The Framingham Study: An
Epidemiologic Investigation of Cardiovascular Disease.
Bethesda, MD. U.S. Department of Health and Human Services,
1987, DHHS publication (NIH) 87-2703.
5 Expert Panel. Report of the National Cholesterol
Education Program Expert Panel on Detection, Evaluation and
Treatment of High Blood Cholesterol in Adults. Arch Intern
Med 1988; 148:36-39.
6 Frick MH, Elo O, Heinonen O, et al. Helsinki Heart Study:
Primary-prevention trial with gemfibrozil in middle-aged men
with dyslipidemia. Safety of treatment, changes in risk
factors, and incidence of coronary heart disease. N Eng J
Med 1987; 317:1237-1245.
7 Frommer PL, Verter J, Wittes J, Castelli W. Cholesterol
reduction and life expectancy. Ann Intern Med 1988; 180:
313-314.
8 Gordon DJ, Rifkind BR. Treating high blood cholesterol in
the older patient. Am J Cardiol 1989; 63:48H-52H.
9 Kinosian BP, Eisenberg JM. Cutting into cholesterol.
Cost-effective alternatives for treating
hypercholesterolemia. JAMA 1988; 259:2249-2254.
10 Lipid Research Clinics Program. The Lipid Research
Clinics Coronary Primary Prevention Trial results. I.
Reduction in incidence of coronary heart disease. JAMA 1984;
251:351-364.
11 NIH Consensus Conference: Lowering blood cholesterol to
prevent heart disease. JAMA 1985; 253:2080-2086.
12 Oster G. Epstein AM. Cost-effectiveness of
antihyperlipemic therapy in the prevention of coronary heart
disease. The case of cholestyramine. JAMA 1987; 285:2381-
2387.
13 Stamler J, Wentworth D, Neaton JD. Is relationship
between serum cholesterol and risk of premature death from
coronary heart disease continuous and graded? Findings in
356,222 primary screenees of the Multiple Risk Factor
Intervention Trial (MRFIT). JAMA 1986; 256:2823-2828.
14 Taylor WC, Pass TM, Shepard DS, Komroff AL. Cholesterol
reduction and life expectancy. A model incorporating
multiple risk factors. Ann Intern Med 1987; 106:605-614.
15 Weinstein MC, Coxson PG, Williams LW, Pass TM, Stason WB,
Goldman L. Forecasting coronary heart disease incidence,
mortality, and cost: the coronary heart disease policy model.
Am J Publ Health 1987; 1417-1426.
OBJECTIVES AND SCOPE
The goal of this RFA is to facilitate the evaluation of
potential alternative strategies of cholesterol-lowering by
developing quantitative models of their potential societal
benefits and costs. Research proposals might include but are
not limited to the following approaches:
o Analyses of the association of cholesterol levels with
survivorship, using long-term, as well as short-term,
observational data.
o Analyses of the beneficial and adverse effects of various
cholesterol-lowering regimens on morbidity, disability and
quality of life, as well as life expectancy.
o Analyses using intervention data from randomized trials as
well as observational studies to model the effect of
cholesterol-lowering on morbidity and mortality at different
ages.
o Comparisons of potential health effects and costs of
alternative cholesterol-lowering strategies and other
modalities for CHD prevention.
o Identification of cholesterol-lowering strategies that
might be particularly suitable (or unsuitable) for different
segments of the population (e.g., women, the elderly,
patients with existing CHD, other high-risk patients).
It is anticipated that this research will draw on existing
data, rather than on the collection of new data. The
emphasis will be on encouraging a variety of methodologic
approaches with the broadest possible database and minimal
reliance on unsupported assumptions. Applicants should
therefore specify in detail the questions upon which their
research will focus, their methodologic approach(es) to the
questions, and how they propose to validate their approaches
using existing data. Applicants should also document access
to the data they propose to analyze and provide a detailed
project plan and timetable.
Collaboration among grantees and NHLBI staff is encouraged to
foster coordination of efforts and cross-fertilization of
ideas. To this end, it is anticipated that annual meetings
of grantees will be convened by program staff. Applicants
should include a statement indicating their willingness to
collaborate with other grantees and with NHLBI staff.
A final report providing a detailed summary of the results
obtained in the program is expected at the end of the funding
period. The individual and combined reports may be provided
by the NHLBI to the National Cholesterol Education Program,
for their consideration in future deliberations on treatment
of high blood cholesterol.
MECHANISM OF SUPPORT
The support mechanism for this program will be the
traditional, individual research grant (RO1). Although
approximately $300,000 for this program is included in the
financial plans for fiscal year 1991, award of grants
pursuant to this RFA is contingent upon receipt of funds for
this purpose. It is anticipated that two to four grants will
be awarded under this program. The specific amount to be
funded, however, will depend on the merit and scope of the
applications received and the availability of funds. Since a
variety of approaches would represent valid responses to
this announcement, it is anticipated that there will be a
range of costs among individual grants awarded. While
multi-disciplinary approaches are encouraged it is not the
intent of this announcement to solicit applications for large
studies encompassing a variety of independent projects, i.e.,
program projects. If collaborative arrangements involve
sub-contracts with other institutions, the NHLBI Grants
Operations Branch should be consulted regarding procedures to
be followed (telephone (301) 496-7255).
Upon initiation of the program, the Division of Heart and
Vascular Diseases will sponsor periodic meetings to encourage
exchange of information among investigators who participate
in this program. In the budget for the grant application,
applicants should request ADDITIONAL TRAVEL FUNDS for a one-
day meeting each year, most likely to be held in Bethesda,
Maryland. Applicants should also include a statement in
their applications indicating their willingness to
participate in these meetings.
Applicants, who will plan and execute their own research
programs, are requested to furnish their own estimates of the
time required to achieve the objectives of the proposed
research project. Up to two years of support may be
requested. At the end of the official award period, renewal
applications may be submitted for peer review and competition
for support through the regular grant program of the National
Institutes of Health (NIH). It is anticipated that support
for the present program will begin in March 1991.
Administrative adjustments in project period and/or amount of
support may be required at the time of the award.
All current policies and requirements that govern the
research grant programs of the NIH will apply to grants
awarded under this RFA. Awards under this announcement to
foreign institutions will be made only for research of very
unusual merit, need and promise, and in accordance with
Public Health Service policy governing such awards.
REVIEW PROCEDURES AND CRITERIA
Review Methods: All applications submitted in response to
this RFA will be evaluated for scientific and technical merit
by an initial review group, which will be convened for this
purpose by the Division of Extramural Affairs, NHLBI. Upon
receipt, applications will be reviewed for their
responsiveness to the objectives of this RFA. If an
application is judged unresponsive, the applicant will be
contacted and given the opportunity to withdraw the
application, or have it considered for the regular NIH grant
program. If an application submitted in response to this RFA
is substantially similar to an application already submitted
to the NIH for review, the applicant will be required to
withdraw the pending application before the new one is
accepted. Simultaneous submission of substantially similar
applications will not be allowed.
Review Criteria: The factors to be considered in the
evaluation of scientific merit of each application will be
similar to those used in the review of traditional research
project grant applications, including:
o the scientific merit of the proposed project, including
the relevance and importance of the research questions and
the originality, feasibility, and soundness of the proposed
methodologic approach(es);
o the competence of the investigator(s) to accomplish the
proposed research goals, and the effort that they will devote
to the project;
o the adequacy of the facilities for the proposed research;
o documentation that the principal investigator will have
access to the data to be analyzed;
o demonstration that the investigator(s) understand the
extent and limits of the original data base, and how they
affect the proposed research;
o willingness to exchange information and data with other
investigators involved in similar research projects, if
appropriate, and with the NHLBI.
METHOD OF APPLICATION
Letter of Intent: Prospective applicants are asked to submit
a letter of intent to apply to this RFA. This letter should
include the name of any participating institutions and all
investigators, together with a descriptive title. Such a
letter of intent is not binding, and it will not enter into
the review of any application subsequently submitted, nor is
it a necessary requirement for application. Letters of
intent are requested solely for planning purposes. The NHLBI
Staff will not provide responses to such letters. Letters of
intent to apply to this RFA should be received no later than
May 11, 1990 and should be addressed to:
Dr. James Scheirer
Review Branch
Division of Extramural Affairs
National Heart, Lung and Blood Institute
National Institutes of Health
Westwood Building, Room 548-B
Bethesda, Maryland 20892
Format for Applications: Submit applications on form PHS 398
(Revised 10/88), the application form for the traditional
research project grant. Copies of this form are available in
the applicant institution's office of sponsored research, or
may be obtained from the following:
Office of Grants Inquiries
Division of Research Grants
Westwood Building, Room 449
Bethesda, Maryland 20892
Use the conventional format for research project grant
applications and ensure that the points identified in the
section above on "Review Procedures and Criteria" are
fulfilled. To identify the application as a response to the
RFA, CHECK "YES" on item 2 of page 1 of the application and
enter the title "Cost-Effective Strategies of Cholesterol-
Lowering" and enter the RFA number NIH 90-HL-5-H in the space
provided.
THE RFA LABEL FOUND IN THE FORM PHS-398 APPLICATION KIT MUST
BE AFFIXED TO THE BOTTOM OF THE FACE PAGE OF THE ORIGINAL
COMPLETED APPLICATION FORM PHS-398. 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.
Application Procedure: Send or deliver the completed, signed
application and four (4) complete photocopies of it to the
following office, making sure that the original application with the
RFA label attached is on top:
Division of Research Grants
Westwood Building, Room 240
National Institutes of Health
Bethesda, Maryland 20892**
SEND TWO ADDITIONAL COPIES OF THE APPLICATION TO DR. JAMES
SCHEIRER AT THE ADDRESS LISTED UNDER "LETTER OF INTENT." IT
IS IMPORTANT TO SEND THESE TWO COPIES AT THE SAME TIME AS THE
ORIGINAL AND FOUR COPIES ARE SENT TO THE DIVISION OF RESEARCH
GRANTS, OTHERWISE THE NHLBI CANNOT GUARANTEE THAT THE
APPLICATION WILL BE REVIEWED IN COMPETITION FOR THIS RFA.
Applications must be received by June 19, 1990. An
application not received by this date will be considered
ineligible.
Timetable:
Letter of intent May 11, 1990
Receipt of application June 19, 1990
Review by the National Heart, Lung,
and Blood Advisory Council February 14-5, 1991
Anticipated award date March 1, 1991
Inquiries: Inquiries regarding this announcement may be
directed to the following:
David J. Gordon, M.D., Ph.D.
Lipid Metabolism-Atherogenesis Branch
Division of Heart and Vascular Diseases
National Heart, Lung and Blood Institute
National Institutes of Health
Federal Building, Room 401
7550 Wisconsin Avenue
Bethesda, MD 20892
Telephone: (301) 496-1681