kristoff@GENBANK.BIO.NET (Dave Kristofferson) (03/17/90)
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