DATA COORDINATING CENTER FOR THE SLEEP HEART HEALTH STUDY

Release Date: February 11, 1999

RFA:  HL-99-014

P.T.

National Heart, Lung, and Blood Institute

Letter of Intent Receipt Date:  March 1, 1999
Application Receipt Date:  March 25, 1999

PURPOSE

The purpose of this initiative is to solicit applications for a new Data
Coordinating Center (DCC) for the Sleep Heart Health Study (SHHS).  The SHHS
is a multi-center, epidemiological investigation to assess sleep apnea as an
independent or contributing risk factor for the development of cardiovascular
and cerebrovascular disease. The SHHS utilizes existing cardiovascular
cohorts, to examine whether sleep-disordered breathing (SDB) is associated
with an increased risk of incident coronary heart disease events, incident
stroke, increase in blood pressure and increased risk of all cause mortality. 
The SHHS has completed home sleep studies on over 6,400 subjects and has begun
to analyze these data in relationship to existing cardiovascular outcomes. 
The next competitive phase of the program will continue to address the primary
hypothesis through repeat sleep studies and follow-up.

A single DCC will support protocol development, sample size calculations,
common questionnaires, complete data analysis, data management,
standardization of procedures, quality control, development of analytical
models, utilization of extensive longitudinal data from cardiovascular
epidemiological cohorts, and overall study coordination required by the multi-
center research program under the cooperative agreement mechanism (U01).  This
announcement is to invite applications for a DCC from all potential
applicants.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of "Healthy People 2000," a PHS-led national
activity for setting priority areas.  This RFA, Data Coordinating Center for
the Sleep Heart Health Study, is related to the priority areas of heart
disease and stroke, clinical prevention services, diabetes and chronic
disabling diseases.  Potential applicants may obtain a copy of "Healthy People
2000" (Full Report:  Stock No. 017-001-00474-0 or Summary Report:  Stock No.
017-001-00473-1) through the Superintendent of Documents, Government Printing
Office, Washington, DC 20402-9325 (telephone 202-512-1800). It may also be
found at http://www.crisny.org/health/us/health7.html.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic organizations, for-profit and
non-profit, public and private, such as universities, colleges, hospitals,
laboratories, units of state and local governments, and eligible agencies of
the Federal government.  Foreign organizations may not apply as the
coordinating center for this program should reside within the U.S. in order to
provide the resources to the U.S. clinical centers as well as ready access and
familiarity with existing longitudinal data from other cardiovascular disease
populations and cohorts.  Racial/ethnic minority individuals, women, and
persons with disabilities are encouraged to apply as Principal Investigators. 
Applicant organizations should have experience functioning as a statistical
coordinating center for multi-site clinical research of a medical and/or
behavioral nature.

The principal investigator of an existing SHHS clinical center may not apply
for the DCC to ensure that data analysis is done independently of data
acquisition.  However, individuals other than the principal investigator of
the SHHS center at the same institution may apply for the DCC award.  Data
coordinating centers currently involved with epidemiology cohort studies are
eligible.

MECHANISM OF SUPPORT

This RFA will use the cooperative agreement (U01) administrative and funding
mechanism of support.  Under the cooperative agreement, the NIH assists,
supports, and/or stimulates, and is substantially involved with recipients in
conducting a study by facilitating performance of the effort in a "partner"
role.  Details of the responsibilities, relationships, and governance of a
study funded under a cooperative agreement are discussed later in this
document under the section entitled RESEARCH OBJECTIVES.

The total project period for applications submitted in response to this RFA
may not exceed 5 years. This RFA is a one-time solicitation.  The anticipated
start date is September 30, 1999.

FUNDS AVAILABLE

It is anticipated that one award for a DCC will be made.  Applicants may
request a project period of up to 5 years and a budget for total costs of
$700,000 in the first year.  Any sub-contract costs and F&A costs should be
included in this total amount.  Facilities and administrative costs (formally
indirect costs) will be awarded based on the grantee's negotiated rate. 
Future year annual increments in direct costs are not to exceed three percent. 
Although the financial plans of the NHLBI provide support for this program,
awards pursuant to this RFA are contingent upon the availability of funds and
the receipt of a sufficient number of applications of outstanding scientific
and technical merit.  Designated funding levels are subject to change at any
time prior to final award, due to unforeseen budgetary, administrative, or
scientific developments.  Funding of the DCC will be contingent upon
successful competitive renewal and funding of the SHHS clinical centers.

RESEARCH OBJECTIVES

A. Background

There has been accumulating evidence over the past several years that sleep
apnea leads to alterations in the cardiovascular system, which may predispose
to morbid cardiovascular events and even sudden death.  Results from
population-based studies suggest that sleep-disordered breathing, ranging from
mild to moderate severity, is an independent risk factor for hypertension and
elevated blood pressure during both wakefulness and sleep.  Furthermore, the
relative risks of ischemic heart disease, myocardial infarctions and
cerebrovascular accidents range from 1.5 to 4 in snorers as compared to non-
snorers.  Hypertension is common in patients with sleep apnea; other studies
suggest that up to 40% of hypertensive patients may have significant sleep
apnea.  Improvement in hypertension control has been reported to occur in
patients with both conditions following treatment of their apnea. 
Cardiovascular mortality may be significantly higher among untreated or
conservatively treated patients with sleep apnea compared to aggressively
treated patients.

Sleep apnea may be an independent cardiovascular disease risk factor, a
concomitant of established cardiovascular or cerebrovascular diseases or other
risk factors (such as obesity or hypertension), but this remains to be
determined.  Similarly, little is known regarding potential interactions
between sleep apnea and other risk factors, or whether specific population
subgroups may be particularly susceptible to adverse cardiovascular and
cerebrovascular consequences potentially associated with sleep apnea.  The
profound physiological derangements (hypoxemia, severe hypertension,
tachycardia, fragmentation of sleep, arrhythmias) that often occur in
association with sleep-disordered breathing provide biologically plausible
explanations for associations between sleep apnea and cardiovascular
morbidity.

Although the limited epidemiological studies are suggestive of sleep apnea as
a potential risk factor for systemic hypertension, a direct etiologic link
between the two disorders and the specific physiologic mechanisms has been
difficult to demonstrate.  The combination of the epidemiological evidence
demonstrating more night time cardiovascular abnormal events in persons with
mild asymptomatic sleep apnea, coupled with animal model data, implies that
there is a causal relationship between sleep apnea and cardiovascular disease. 
The high prevalence of both disorders in the population suggest that sleep
apnea may be a potential modifiable risk factor for the prevention of heart
disease and stroke.

Identification of factors that predispose to increased risk for sleep apnea is
important for public health policy.  It will allow specific high risk
populations to be targeted and provide an improved understanding of disease
pathogenesis that may include interactions among a number of risk factors.

The SHHS has established a highly interactive, coordinated group of clinical
centers working under a common protocol to investigate these relationships. 
The initial study was established in 1994 with six clinical centers and one
data coordinating center.  During the initial 5 year period, home sleep
studies have been conducted on more than 6,400 subjects.  Data analysis and
publication of the initial cross sectional findings are underway.  The
clinical centers have submitted competitive renewal applications to continue
to test the primary hypothesis through repeat sleep studies and longitudinal
follow up.

B. Objectives and Scope

The overall objective of the SHHS is to utilize existing, well characterized,
population-based epidemiologic cohorts (parent studies) to determine the
degree to which sleep apnea is an independent or contributing risk factor for
the development of cardiovascular and cerebrovascular disease.  It is also
aimed at examining possible associations between sleep apnea, hypertension and
stroke within different age, gender and racial/ethnic groups.  This program
has five specific aims.

o  Determine the risk of cardiovascular disease (CVD) associated with sleep
apnea and other sleep related breathing disorders independent of other
cardiovascular disease risk factors;

o  Assess potential interactions between sleep apnea and other vascular
disease risk factors, particularly obesity and hypertension, in relation to
CVD risk;

o  Examine the contribution of sleep apnea to the development of other CVD
risk factors, particularly hypertension;

o  Identify population subgroups at greatest risk for adverse clinical
outcomes from sleep apnea including those defined by age, gender and race;

o  Estimate the extent of medical care utilization, health care costs, and
measures of quality of life associated with sleep apnea.

These aims are designed to test four primary hypotheses developed by the SHHS
investigators.

o Sleep-disordered breathing is associated with an increased risk of incident
coronary heart disease events.

o Sleep-disordered breathing is associated with an increased risk of incident
stroke.

o Sleep-disordered breathing is associated longitudinally with increased blood
pressure.

o Sleep-disordered breathing is associated with increased risk of all-cause
mortality.

Although these are the primary hypotheses to be tested by the SHHS, others may
be appropriate and the program is not restricted to the primary hypotheses
listed above.  A number of secondary hypotheses will be tested either on the
entire cohort or subsets where appropriate covariate data exist.  Information
about protocols, hypotheses, ancillary and substudies, the SHHS Manual of
Operations, the Reading Center Manual of Operations and the characteristics of
study datasets can be obtained by contacting the scientific project officer
listed under INQUIRIES.  Some of this information is also available from the
SHHS home page at:  http://140.142.220.29/shhs/

SHHS Design

The SHHS cohort was established by recruiting a sample of snorers and non-
snorers from existing NHLBI-supported cohorts, including the Atherosclerosis
Risk in Communities Study (ARIC), the Cardiovascular Heart Study (CHS), the
Strong Heart Study (SHS), the Framingham Heart Study (FHS), the Tucson
Epidemiologic Study of Obstructive Airways Disease, the Tucson Health and
Environment Cohort, and three New York cohorts.  In total, 6,400 subjects from
10 clinical sites and six administrative entities were recruited and completed
a baseline sleep study.  Data  previously collected by the existing parent
studies provided baseline (prior to the sleep study)  information on
hypertension, obesity, and other cardiovascular risk factors, and prevalent
cardio/cerebrovascular disease.  Polysomnography variables, collected by
unattended multi-channel sleep studies, were obtained on cohort members
following a standardized home visit protocol.  A reading center, located at
Case Western University was responsible for evaluation and quality grading of
all polysomnography (PSG) data.  Key data not collected for any given cohort,
and data that could vary over time and influence interpretation of the sleep
study or the relationship of the sleep variables with cardiovascular outcomes,
also were directly measured or assessed during the home visit.  The
comparability between cohorts and sites of all key predictor and outcome data
obtained from the parent studies was assessed.  Follow-up data, including
cardiovascular outcomes, were assessed in 18 to 36 month follow-up visits and
telephone calls.  Sub-studies were performed to assess scoring reliability,
night to night variability of sleep studies, and comparability of laboratory
and home-based sleep studies; the relationship of measured urinary
catecholamines and SDB; and the relationship of SDB with neuropsychological
functions.  A large amount of covariate and outcome data has been collected
from the parent cohorts.

The proposed plans for continuation of SHHS call for collection of additional
follow-up data to provide statistical power to assess the relationship of SDB
with incident cardiovascular diseases. Other objectives likely will include:
follow-up sleep studies to describe the change in SDB over time, and the
impact of change in SDB indices with incident cardiovascular disease;
functional outcomes (sleepiness, general health and functional status); and
assessment of pathophysiological processes that may mediate cardiovascular
diseases associated with SDB, and identification of interactions between SDB
and other risk factors in the development of CVD.

Morbid outcomes may be defined with the use of several measures, such as
evidence of left ventricular dysfunction, sustained hypertension,
atherosclerosis, cognitive impairment, hospital admissions for  treatment of
ischemic heart disease, health care expenditures associated with CVD and
cerebrovascular disease, measures of  functional status, quality of life, and
death.

Data Coordinating Center Design

Applications should present a plan for a data coordinating center which
includes approaches to the following activities and any others that would
complement the functions outlined below.  All plans should be compatible with
procedures and requirements outlined in the SHHS Manual of Operations.  It is
anticipated that the plans of the successful DCC application will be submitted
to the SHHS steering committee for further consideration and that final plans
will be developed once the cooperative agreement has been awarded.  A decision
to fund a particular DCC application will not commit the SHHS steering
committee to conduct the specific plans outlined in that application.

For any activities to be conducted through subcontracts, applicants should
develop and describe such operational factors as access to subjects,
organization of the facility, means of assuring quality control, data entry,
plans for coordination, and a process for filing human subject assurances.

1) Data Coordination

a.  Assume responsibility for the common database currently in existence to
which all SHHS clinical centers contribute demographic, clinical,
physiological, and pathological information about subjects in a standard
format.  The DCC is expected to provide leadership with respect to the
orderly, timely, accurate accumulation and transmission of these data.  Plans
should include, but are not limited to, designing efficient systems for
collecting and managing data, operational and management structures providing
lines of responsibility and staffing for DCC functions across the life of the
study;  tracking and implementation of established study protocols and
proposed analyses as described in the SHHS Manual of Operations; calculations
for operational costs for all DCC functions; data acquisition, transfer, and
management; the tabulation of survey instruments such as the Sleep Habits
Questionnaire; printing and distribution of study protocols; report
preparation; data archiving and backups of study data; maintain and expand
SHHS web site; and duplication for storage at each clinical site.

b.  Using the data collected before the sleep study will require state-of-the-
art longitudinal data analysis techniques.  Approaches will be needed to use
previously collected information. For example, modeling approaches will be
needed to address the natural history of sleep-disordered breathing and its
relationship with CVD risk.  Applicants should be familiar with approaches for
analysis of longitudinal data on blood pressure and time-varying predictors of
CVD occurrence.  Also, expansion of the common database to use existing data
from the parent cohorts or collect cohort-specific data for comparisons that
could be important to the study objectives such as the identification of
prevalent cardiovascular disease and hypertension, lung function abnormalities
(spirometry), and potential confounders such as body weight, smoking, and
medications.  Expansion will entail surveying parent cohort database
structures; proposing ways to facilitate and integrate common variables and
index non-conforming variables in the common database; time lines for
completion of data migration; establish a database to collect and maintain
parent cohort endpoint data and develop procedures for adjudication of the
major study endpoints; and working with the sleep reading center for quality
control.  Provide leadership in addressing complex analysis issues, including
data comparability issues, and interactions between sleep variables and other
risk factors in relation to CVD risk; longitudinal data analysis and model
development; innovative uses of the extensive CVD data collected from various
population-based studies; oversee quality control activities.

c.  Plans and time line for the orderly transfer of SHHS data, documentation
and programs from the incumbent DCC to the new DCC.  Also, transfer of data to
the NHLBI or another DCC at the end of the funding period.

d.  Plans to facilitate DCC participation in further data sharing efforts and
studies using the databases.

e.  Training programs to educate DCC and SHHS staff about operating procedures
with the goal of maximizing efficiency and accuracy in data operations. 
Establish quality control procedures including those for field center
technicians for protocol adherence and home data collection.

f.  Procedures to work with the Reading Center to assure data quality and
confidentiality of subjects.

g.  Procedures to disseminate data available in the DCC.

h.  Provide administrative support and participate in steering committee and
subcommittee activities, including maintaining a database to track proposed
and active manuscripts and interact with parent studies for clearance of all
publications.

i.  Provide statistical advice and consultation on study design to
investigators involved in studies approved by the SHHS Steering Committee and
to encourage maximum use of data collected by the DCC.  Assume primary
responsibility for all statistical analysis.

2) Interactions with Sleep Reading Center

Coordination of all data collection and analyses integrally involve PSG data
uniquely designed  for SHHS.  It is anticipated that because of the complexity
of the PSG data, and procedures already developed for managing these data, and
to minimize the need for the new DCC to learn all the details of the PSG data,
the Reading Center will assume responsibility for the preliminary analysis,
clean-up, storage, archiving and reporting polysomnography data for the main
purpose of processing, tracking performance and PSG quality control.  The
Reading Center will transfer data to the DCC, which will be responsible for
overall quality control procedures and primary statistical analyses as well as
general study logistics (organization of subcommittees, meeting logistics,
generation of forms, collation of data from parent cohorts, and collection of
data from survey instruments/questionnaires).

3) Coordination of meetings and reports

a.  Administratively support the SHHS steering committee, which includes the
principal investigator of the DCC; the principal investigator of individual
clinical centers and the reading center; specialized external consultants; the
Data Safety and Monitoring Board (DSMB), and NHLBI staff.  The steering
committee must be kept informed and approve of any changes in policy.

b.  Organize and provide administrative support including preparing the
minutes for meetings and teleconferences called for by the SHHS steering
committee or its sub committees to monitor operations; approve changes in
procedures; and facilitate other coordination activities.

c.  Prepare regular reports as defined in SHHS Manual of Operations, or 
requested by the SHHS steering committee, sub committees, and NHLBI staff.

SPECIAL REQUIREMENTS

Terms and Conditions of Award

The cooperative agreement is an award instrument establishing an "assistance" 
relationship (in contrast to an "acquisition" relationship) between NHLBI and
a recipient, in which substantial NHLBI scientific and/or programmatic
involvement with the recipient is anticipated during performance of the
activity.  The NHLBI purpose is to support and/or stimulate the recipient's
activity by involvement in and otherwise facilitating the activity in a
"partner" role, but avoiding a dominant role, direction, or prime
responsibility.  The terms and conditions, below, elaborate on these actions
and responsibilities, and the awardee agrees to these collaborative actions
with the NHLBI Project Scientist toward achieving the project objectives.  It
is anticipated that these terms and conditions will enhance the relationship
between the NHLBI staff and the principal investigator(s), and will facilitate
the successful conduct and completion of the study.  These agreements will be
in addition to, and not in lieu of, the relevant NIH procedures for grants
administration.  The terms will be as follows:

1.  The awardee(s) will have lead responsibilities in all aspects of their
protocols, including any modification of study design, conduct of the study,
quality control, data analysis and interpretation, preparation of
publications, and collaboration with other investigators, unless otherwise
provided for in these terms or by action of the Steering Committee.

2.  The NHLBI Project Scientist will serve on the Steering  Committee; he/she
or another NHLBI scientist may serve on other study committees, when
appropriate.  The NHLBI Project Scientist (and the other cited NHLBI
scientists) may work with awardees on issues coming before the Steering
Committee and, as appropriate, other committees, e.g.,  recruitment,
intervention, follow-up, quality control, adherence to protocol, assessment of
problems affecting the study and potential changes in the protocol, interim
data and safety monitoring, final data analysis and interpretation,
preparation of publications, and development of solutions to major problems
such as insufficient participant enrollment.

3.  Awardee(s) agree to the governance of the study through a Steering
Committee. Steering Committee voting membership shall consist of the principal
investigators (i.e., cooperative agreement awardees) and the NHLBI Project
Scientist.  Meetings of the Steering Committee will ordinarily be held by
telephone conference call or in the Washington DC Metropolitan Area.

4.  A Data and Safety Monitoring Board will be appointed by the Director,
NHLBI to provide overall monitoring of interim data and safety issues; the
Steering Committee will nominate members for this Board.  Meetings of the Data
and Safety Monitoring Board will ordinarily be held in Bethesda, MD.  The
NHLBI Project Scientist shall serve as Executive Secretary to the Board..

5.  Awardees will retain custody of and have primary rights to their data
developed under these awards, subject to Government rights of access
consistent with current HHS, PHS, and NIH policies.  The collaborative
protocol and governance policies will call for the continued submission of
data centrally to the coordinating center for a collaborative database; the
submittal of copies of the collaborative data sets to each principal
investigator upon completion of the study; procedures for data analysis,
reporting and publication; and procedures to protect and ensure the privacy of
medical and genetic data and records of individuals.  The NHLBI Project
Scientist, on behalf of the NHLBI, will have the same access, privileges and
responsibilities regarding the collaborative data as the other members of the
Steering Committee.

6.  Support or other involvement of industry or any other third party in the
study -- e.g., participation by the third party;  involvement of project
resources or citing the name of the project or the NHLBI support; or special
access to project results, data, findings or resources -- may be advantageous
and appropriate.  However, except  for licensing of patents or copyrights,
support or involvement of any third party will occur only following
notification of and  concurrence by NHLBI.

7.  Awardees are encouraged to publish and to publicly release and disseminate
results, data and other products of the study, concordant with the study
protocol and governance and the approved plan for making data and materials
available to the scientific community and the NHLBI.  However, during or
within three years beyond the end date of the project period of  NHLBI
support, unpublished data, unpublished results, data sets not previously
released, or other study materials or products are to be made available to any
third party only with the approval of the Steering Committee and in accordance
with paragraph 6.

8.  Upon completion of the project, the Data Coordinating Center is expected
to put all study intervention materials and procedure manuals into the public
domain and/or make them available to other investigators, according to the
approved plan for making data and materials available to the scientific
community and the NHLBI, for the conduct of research at no charge other than
the costs of reproduction and distribution.

9.  The NHLBI reserves the right to terminate or curtail the study (or an
individual award) in the event of  (a) failure to develop or implement a
mutually agreeable collaborative protocol,  (b) substantial shortfall in
participant recruitment, follow-up, data reporting, quality control, or other
major breach of the protocol, (c) substantive changes in the agreed-upon
protocol with which NHLBI cannot concur, (d) reaching a major study endpoint
substantially before schedule with persuasive statistical significance, or (e)
human subject ethical issues that may dictate a premature termination.

10.  Any disagreement that may arise in scientific/programmatic matters
(within the scope of the award), between award recipients and the NHLBI may be
brought to arbitration.  An arbitration panel will be composed of three
members--one selected by the Steering Committee (with the NHLBI member not
voting) or by the individual awardee in the event of an individual
disagreement, a second member selected by NHLBI, and the third member selected
by the two prior members.  This special arbitration procedure in no way
affects the awardee's right to appeal an adverse action that is otherwise
appealable in accordance with the PHS regulations at 42 CFR part 50, Subpart D
and HHS regulation at 45 CFR part 16, or the rights of NHLBI under applicable
statutes, regulations and terms of the award.

11.  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 policy statements.
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and
their subpopulations must be included in all NIH supported biomedical and
behavioral research projects involving human subjects, unless a clear and
compelling rationale and justification is provided that inclusion is
inappropriate with respect to the health of the subjects or the purpose of the
research.  This policy results from the NIH Revitalization Act of 1993
(Section 492B of Public law 103-43).

All investigators proposing research involving human subjects should follow
the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research," which have been published in the Federal Register of March
28, 1994 (FR 59 14508-14513), and reprinted in the NIH Guide for Grants and
Contracts of March 18, 1994, Volume 23, Number 11 and available on the web at:
http://www.nih.gov/grants/guide/1994/94.03.18/notice-nih-guideline008.html.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that children (i.e., individuals under the age of
21) must be included in all human subjects research, conducted or supported by
the NIH, unless there are scientific and ethical reasons not to include them. 
This policy applies to all initial (Type 1) applications submitted for receipt
dates after October 1, 1998.

All investigators proposing research involving human subjects should read the
NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects that was published in the NIH Guide for
GRANTS and Contracts, March 6, 1998, and is available at the following URL
address: http://www.nih.gov/grants/guide/notice-files/not98-024.html.

Investigators also may obtain copies of these policies from the program staff
listed under INQUIRIES.  Program staff may also provide additional relevant
information concerning the policy.

LETTER OF INTENT

Prospective applicants are asked to submit, by March 1, 1999 a letter of
intent that includes a descriptive title of the proposed research, the name,
address, and telephone number of the Principal Investigator, the identities of
other key personnel and participating institutions, and the number and title
of this RFA.  Although a letter of intent is not required, is not binding, and
does not enter into the review of subsequent applications, the information
that it contains is helpful in planning for the review of applications.  It
allows NHLBI staff to estimate the potential review workload and to avoid
conflict of interest in the review.

The letter of intent is to be faxed or sent to Dr. C. James Scheirer at the
address listed under INQUIRIES.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in
applying for these grants.  These forms are available at most institutional
offices of sponsored research and may be obtained from the Division of
Extramural Outreach and Information Resources, National Institutes of Health,
6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301-435-
0714, Email: GrantsInfo@nih.gov.  The PHS 398 application kit is also
available on the Internet at http://www.nih.gov/grants/forms.htm

Additional Material to Include in the Application:

It is envisioned that the Principal Investigator (PI) will be an established
investigator in biostatistical, epidemiological, cardiovascular, pulmonary, or
sleep disorders research with prior experience in complex, large-scale
collaborative studies and the delivery of logistical support.  It would be
desirable for the PI and/or key investigators to have relevant expertise in
cardiovascular disease risk factors, epidemiology, and/or sleep disorders
medicine.  It is not essential that this investigative team be from the same
institution.  However, if applications involve investigators from different
institutions there must be well documented plans for adequate communication,
interactions, and facilities to perform analytic and other activities
required.  The PI must commit a minimum of 20% effort to the DCC.

Applicants must demonstrate familiarity with the structure and operations of
the SHHS, and be able to interact effectively with Clinical Centers and the
reading center using  protocols for data exchange and quality control
management outlined in the SHHS Manual of Operations.  Additional technical
information on the operational aspects of the current DCC and specific
information for data transfer and documentation can be obtained by contacting
the program official listed under INQUIRIES.  Applicants should also state
their willingness, and that of the institutions involved, to participate in a
cooperative and interactive manner with the SHHS Clinical Centers and the
NHLBI within the context of this collaborative research program.  Applicants
from institutions that have a General Clinical Research Center (GCRC) funded
by the NIH National Center for Research Resources may wish to identify the
GCRC as a resource for conducting the proposed research.  In such a case, a
letter of agreement from either the GCRC Program Director or Principal
Investigator should be included with the application.

Data Coordinating Center applicants should discuss their perception of the DCC
role in the SHHS, various aspects of study design, their familiarity with
sleep disorders and cardiopulmonary risk factors and diseases, important
considerations for making sample size and power calculations, interpretation
of baseline and outcome measures, monitoring accuracy of data collection,
quality control procedures including training and certification, proposed
modifications to processes used by the incumbent DCC; and plans for
statistical analysis of results.

BUDGET PREPARATION

Applications for DCC should present five budget periods of 12 months each
using the instructions provided with the research grant application form (PHS
398, rev. 4/98).  Applicants are expected to perform all DCC functions with
the funding available through this RFA.  Future year annual increments in
direct costs are not to exceed three percent.

Applicants should provide adequate justification for all applicable direct
costs.  Estimates of staffing needs, including the Principal Investigator, Co-
Investigator, other professional and support staff must be included.  The
suggested level of commitment for the Principal Investigator and Co-
Investigator should be 20 percent each.  Other personnel such as data center
coordinator, data technicians, consultants, and support staff should be
carefully outlined and justified in the application.  Travel costs should be
budgeted for two people to attend 2-3 steering committee meetings in Bethesda
each year.  Funds should be requested to support up to two meetings of the
DSMB each year in Bethesda, MD.  Any major equipment items should be well
justified.  Collaborations or subcontracts that involve the transfer of funds
from the grantee to other institutions require formal subcontract agreements
with each collaborating institution.  Budgets for subcontracts should be
prepared using the same guidelines as for the main grant.  The costs for the
Sleep Reading Center should NOT be included as part of the DCC application. 
The Reading Center will submit a separate application.

The award will be subject to administrative review annually.

Applications not conforming to these guidelines will be considered
unresponsive to this RFA and will be returned without further review.

The RFA label available in the PHS 398 application form must be affixed to the
bottom of the face page of the application.  Failure to use this label could
result in delayed processing of the application such that it may not reach the
review committee in time for review.  In addition, to identify the application
as a response to this RFA, check "YES" in item 2 of page 1 of the application
and enter the title "Data Coordinating Center for the Sleep Heart Health
Study, HL-99-014.

Submit a signed, typewritten original of the application and three signed
photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application must be
sent to Dr. C. James Scheirer at the address listed under INQUIRIES.

Applications must be received by March 25, 1999.  If an application is
received after this date it will be returned to the applicant without review.

The Center for Scientific Review (CSR) will not accept any application in
response to this RFA that is essentially the same as one currently pending
initial review, unless the applicant withdraws the pending application.  The
CSR will not accept any application that is essentially the same as one
already reviewed.  This does not preclude the submission of substantial
revisions of an application already reviewed, but such applications must
include an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR and
for responsiveness by NHLBI.  Incomplete and/or nonresponsive applications
will be returned to the applicant without further review.  Applications that
are complete and responsive to the RFA will be evaluated for scientific and
technical merit by an appropriate peer review group convened by the Division
of Extramural Affairs, NHLBI, in accordance with the review criteria stated
below.  The roster of the initial review group will be available via the NHLBI
home page.

As part of the initial merit review, all applications will receive a written
critique and undergo a review in which only those applications deemed to have
the highest scientific merit, generally the top half of the applications under
review, will be discussed, assigned a priority score, and receive a second
level review by the National Heart, Lung and Blood Advisory Council.

Applicants are expected to address issues identified under APPLICATION
PROCEDURES. Applications will be judged primarily on the scientific quality
and appropriateness of the application, facilities, approach to cost
containment, the discussion of considerations relevant to this RFA, expertise
of the investigators, their capability to perform the work proposed, and a
demonstrated willingness to work as part of the collaborative group and with
the NHLBI program official.

Review Criteria

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.  In
the written comments, reviewers will be asked to discuss the following aspects
of the application in order to judge the likelihood that the proposed research
will have a substantial impact on the pursuit of these goals.  Each of these
criteria will be addressed and considered in assigning the overall score,
weighting them as appropriate for each application.  Note that the application
does not need to be strong in all categories to be judged likely to have major
scientific impact and thus deserve a high priority score.  For example, an
investigator may propose to carry out important work that by its nature is not
innovative but is essential to move a field forward.

o  Significance:  Does this study address an important problem?  If the aims
of the application are achieved, how will scientific knowledge be advanced? 
What will be the effect of these studies on the concepts or methods that drive
this field?

o  Approach:  Are the conceptual framework, design, methods, and analyses
adequately  developed, well-integrated, and appropriate to the aims of  the
project?  Does the applicant acknowledge potential problem areas and consider
alternative tactics?

o  Innovation:  Does the project employ novel concepts, approaches or methods? 
Are the aims original and innovative?  Does the project challenge existing
paradigms or develop new methodologies or technologies?

o  Investigator:  Is the investigator appropriately trained and well suited to
carry out this work?  Is the work proposed appropriate to the experience level
of the principal investigator and key personnel?

o  Environment:  Does the scientific environment in which the work will be
done contribute  to the probability of success?  Do the proposed experiments
take advantage of unique features of the scientific environment or employ
useful collaborative arrangements?  Is there evidence of institutional
support?

In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:

o  Understanding of the scientific, statistical, logistical, and technical
issues underlying multicenter studies, including taking a leadership role in
the area of study design, statistics, logistics, data acquisition and
management, quality control, data analysis, and overall coordination.

o  Adequacy of the proposed plans for acquisition, transfer, management, and
analysis of data; interactions with the sleep reading center; quality control
of data collection and monitoring, and overall coordination of Center
activities.

o  The expertise, training, and experience of the investigators and staff,
including the administrative abilities of the Principal Investigator and
co-investigators, and the time they plan to devote to the program for
effective coordination.

o  The administrative, supervisory, and collaborative arrangements for
achieving the goals of the program, including willingness to cooperate with
the participating Clinical Centers and the NHLBI.

o  Facilities, equipment, subcontracts, and organizational structure to
effectively assist Clinical Centers in implementing the protocol and in data
collection procedures and in overall coordination of study-wide activities.

o  Appropriateness of the budget for the work proposed.

o  The personnel category will be reviewed for appropriate staffing based on
the requested percent effort.  The direct costs budget request will be
reviewed for consistency with the proposed methods and specific aims.

Schedule

Letter of Intent Receipt Date:     March 1, 1999
Application Receipt Date:          March 25, 1999
Review by NHLBI Advisory Council:  September 16, 1999
Anticipated Award Date:            September 30, 1999

AWARD CRITERIA

Applications recommended by the National Heart, Lung, and Blood Advisory
Council will be considered for award based upon (a) scientific and technical
merit, (b) scientific-programmatic requirements, including in this instance,
sufficient compatibility of features to make a successful collaborative
program a reasonable likelihood, and (c) availability of funds.

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

James P. Kiley, Ph.D.
National Center on Sleep Disorders Research
National Heart, Lung, Blood Institute
6701 Rockledge Drive, Suite 10038, MSC-7920
Bethesda, MD  20892-7920
Telephone:  (301) 435-0199
FAX:  (301) 480-3451
Email:  KileyJ@nih.gov

Direct inquiries regarding review matters, address the letter of intent and
send two copies of the completed application to:

C. James Scheirer, Ph.D.
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7220, MSC 7924
Bethesda, MD  20892-7924
Telephone:  (301) 435-0266
FAX:  (301) 480-3541
Email: jslloj@nih.gov

Direct inquiries regarding fiscal matters to:

Raymond L. Zimmerman
Grants Operations Branch
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7154
Bethesda, MD  20892-7926
Telephone:  (301) 435-0171
FAX:  (301) 480-3310
Email: ZimmermR@gwgate.nhlbi.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance, No.
93.838.  Awards are made under authorization of the Public Health Service Act,
Title IV, Part A (Public Law 78-410, amended by Public Law 99-158, 42 USC 241
and 285) and administered under PHS grants policies and Federal Regulations 42
CFR 52 and 45 CFR Part 74.  This program is
not subject to the intergovernmental review requirements of Executive Order
12372 or a Health Systems Agency Review.

The PHS strongly encourages all grant and contract recipients to provide a
smoke-free workplace and promote the non-use of all tobacco products.  In
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking
in certain facilities (or in some cases, any portion of a facility) in which
regular or routine education, library, day care, health care or early
childhood development services are provided to children.  This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.


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