Full Text HL-93-016

COMMUNITY INTERVENTION TO REDUCE MYOCARDIAL INFARCTION DELAY

NIH GUIDE, Volume 22, Number 22, June 18, 1993

RFA:  HL-93-016-P

P.T. 34

Keywords: 
  Cardiovascular Diseases 
  Community/Outreach Programs 
  Health and Safety Education 
  Treatment, Medical+ 


National Heart, Lung, and Blood Institute

Letter of Intent Receipt Date:  October 12, 1993
Application Receipt Date:  December 21, 1993

PURPOSE

The Division of Epidemiology and Clinical Applications (DECA) invites
applications for cooperative agreements with the National Heart,
Lung, and Blood Institute (NHLBI) for an estimated six Field Sites
and one Coordinating Center for a collaborative multicenter study on
Community Intervention to Reduce Myocardial Infarction Delay.  The
primary objective of this research program is to evaluate the impact
of community educational interventions on patient delay time from
onset of symptoms and signs of an acute myocardial infarction (AMI)
to seeking care for treatment.  Other research objectives are to
study the impact of community educational interventions on use of
Emergency Medical Services and Emergency Departments, on thrombolytic
therapy, and on AMI case fatality.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This Request
for Applications (RFA), Community Intervention to Reduce Myocardial
Infarction Delay, is related to the priority areas of heart disease
and educational and community-based programs.  Potential applicants
may obtain a copy of "Healthy People 2000" (Full Report:  Stock No.
017-001-00474-0) or "Healthy People 2000" (Summary Report:  Stock No.
017-001-00473-1) through the Superintendent of Documents, Government
Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by any domestic for-profit or
non-profit organization.  Any international component of a domestic
application must be minor in its magnitude and critical in what it
would contribute. Applications from minority individuals and women
are encouraged.

Awards for a Field Center and Coordinating Center under this RFA will
not be made to the same Principal Investigator (PI) or team of
investigators to ensure that data analysis is done independently of
data acquisition.  The same institution may apply for both a Field
Site and the Coordinating Center award, but the applications for each
must be from different individuals.

MECHANISM OF SUPPORT

The administrative and funding mechanism to be used to undertake this
program will be a cooperative agreement (U01), which is an
"assistance" mechanism, rather than an "acquisition" mechanism.
Under the cooperative agreement, the NIH purpose is to support and/or
stimulate the recipient's activity by collaborating and otherwise
working jointly with the award recipient in a partner role, but it is
not to assume direction, primary responsibility, or a dominant role
in the activity.  Details of the responsibilities, relationships, and
governance of a study funded under a cooperative agreement are
discussed under the section Terms and Conditions of Award.  See also
FUNDS AVAILABLE below.

FUNDS AVAILABLE

It is estimated that four to eight awards for Field Sites and one
award for a coordinating center will be made under this RFA.
Approximately $11,400,000 (including direct and indirect costs) will
be available over the four year period, including approximately
$2,000,000 during the first year for the Field Sites and $500,000 for
the Coordinating Center.

Awards and level of support are dependent on the receipt of a
sufficient number of applications of high scientific merit.  Because
the nature and scope of the research proposed in response to this RFA
may vary, it is anticipated that the size of awards will vary also.
Although this program is provided for in the financial plans of the
NHLBI awards pursuant to this RFA are contingent upon the
availability of funds for this purpose.

The total project period for applications submitted in response to
the present RFA may not exceed four years.  The anticipated award
date is July 1, 1994.

At this time the NHLBI anticipates that there will not be a renewed
competition after four years.  If the NHLBI does not continue the
program, awardees may submit grant applications through the usual
investigator-initiated grants program.

RESEARCH OBJECTIVES

Background

Despite the decline in coronary heart disease (CHD) mortality, the
U.S. continues to have high ischemic heart disease mortality rates
when compared with other countries (WHO 1988).  High mortality
persists despite technologic advances in available treatments for
CHD, including cardiopulmonary resuscitation and defibrillation for
cardiac arrest, thrombolytic therapy, aspirin, and beta blockade, and
despite efforts at primary prevention (ACC/AHA 1990).  Approximately
1.25 million persons experience a myocardial infarction in the United
States each year, and about 500,000 deaths due to CHD occur each
year, about one-half of which occur suddenly (within 1 hour of onset
of symptoms) (NHLBI 1992).

Since the advent of thrombolytic therapy, early treatment holds
particular promise for decreasing the high mortality from CHD.
Clinical trials have shown that thrombolytic therapy can reduce
mortality by 25 percent for patients treated within the first few
hours of AMI symptoms (Yusuf et al. 1990).  Pooled data from nine
trials indicate that treatment any time from zero to 24 hours after
symptom onset results in lowered mortality rates, with the greatest
reduction in those treated before 6 hours (Grines & DeMaria, 1990).
The earlier the treatment is started after symptom onset, the greater
the reduction in mortality (GISSI 1986, ISIS-2 1987).  In the first
two hours following onset of symptoms, there is a steep decline in
the curve of time to reperfusion versus benefit; the mortality
reduction within these first two hours of symptom onset is thought to
be predominantly a result of myocardial salvage (Braunwald 1989;
Califf et al. 1989; Koren et al. 1985).

Delay in Seeking Treatment for AMI Symptoms

Not everyone who has an AMI who potentially could benefit from
receiving thrombolytic therapy receives such therapy.  One
contributing factor is that many do not seek emergency care in a
timely manner.  Studies of prehospital time show substantial delay
times from symptoms to hospital arrival, with means ranging from 4.6
hours (Moss et al., 1969) to 21-24 hours (Cooper et al. 1986) and
medians ranging from 2 hours (Turi et al. 1986, Rawles & Haites 1988,
Leitch et al. 1989) to 6.4 hours (Cooper et al. 1986).  Transport
time of the EMS is estimated to average from 7 to 22 minutes
(Schroeder et al. 1978, Weilgosz et al. 1988, Gillum et al. 1976),
making a large proportion of prehospital delay attributable to
patient recognition and action.  Because some individuals wait many
hours to days before seeking medical care for symptoms, mean delay
times are significantly longer than median delay times in all
reported studies (Hackett & Cassem, 1969, Schroeder et al. 1978,
Cooper et al. 1986, Rawles & Haites, 1988, Wielgosz et al. 1988,
Hofgren et al. 1988).

A variety of factors have been associated with delay times, but
findings are often inconsistent across studies, perhaps due to
different study populations, methods of data collection, or
definitions.  Characteristics of the symptoms (severity and
suddenness of chest pain), of the patients (age, gender, race,
socio-economic status), of the patient's medical history (past
history of MI, CHD, related conditions), and of actions taken by the
patient (consultation with others) have been examined as possibly
related to delay time.  The literature suggests that sudden onset
pain is associated with shorter delay times, and older age, female
gender, African-American race, and consultation with others about
symptoms are associated with longer delay times.

Although severity of chest pain has had no effect on delay time in
some reports (Hofgren et al. 1988, Maynard et al. 1989), an inverse
relationship between symptom severity and delay times has been cited
(Hackett and Cassem 1969).  Others have reported reduced delay times
when patients experience chest pain suddenly (Alonzo 1986, Schmidt &
Borsch 1989).

The relationship between existing CHD or past medical history and
delay time has not been in the direction one might expect.  A finding
across several studies is that a history of prior MI does not
decrease delay times (Hofgren et al. 1988, Maynard et al. 1989,
Schroeder et al. 1978, Moss et al. 1969, Turi et al. 1986, Hackett &
Cassem 1969).  The presence of angina either has no effect (Wielgosz
et al. 1988, Moss et al. 1969, Turi et al. 1986) or is associated
with longer delay time (Schroeder et al. 1978, Simon et al. 1972).
Both chronic stable angina (Schroeder et al. 1978) and angina
increasing in severity (Simon et al. 1972) are associated with longer
delay times.  The high risk conditions of congestive heart failure
(Moss et al. 1969), diabetes mellitus (Turi et al. 1986, Moss &
Goldstein 1970), and hypertension (Moss et al. 1969, Turi et al.
1986) variably affect delay times.

Some researchers report that age is not associated with delay
(Wielgosz et al, Gilchrist 1973, Simon et al. 1972, Matthews et al.
1983), while others have found older age to be associated with longer
delay (Turi et al. 1986, Maynard et al. 1989, Rawles & Haites 1988).

Turi et al. (1986) found that women delay longer than men in seeking
medical care for AMI symptoms and Alonzo (1986) reported slightly
increased delay times to medical evaluation for women.  Other
investigators have found no relationship between gender and delay
(Moss & Goldstein 1970, Maynard et al. 1989, Schroeder et al. 1978,
Wielgosz et al. 1988, Hackett & Cassem 1969, Simon et al. 1972,
Gilchrist 1973, Matthews et al. 1983).

In three studies, African-Americans were reported to have increased
delay times (Cooper et al. 1986, Alonzo 1986, Clark et al. 1992).
The longer mean delay time in the Clark et al. (1992) study was due
to a high percentage of patients with delays longer than 24 hours in
blacks and Hispanics.  Other racial groups have not been studied
adequately.

Investigators who have examined the effect of socioeconomic status on
pre-hospital delay have concluded it has no effect (Wielgosz et al.
1988, Hackett & Cassem 1969, Gilchrist 1973, Matthews et al. 1983),
yet in one study, low income was an independent predictor of
increased pre-hospital delay (Schmidt & Borsch 1989).  Education
level has not been associated with delay time (Wielgosz et al. 1988,
Moss et al. 1969, Turi et al. 1986, Simon et al. 1972, Schmidt &
Borsch 1989, Moss & Goldstein 1970).

Consulting with a spouse or unrelated individuals is associated with
significant higher delay times (Alonzo 1986), as is consulting with a
physician (Leitch et al. 1989).  Finally, self-treatment for symptoms
results in a significant increase in delay (Turi et al. 1986).

Interventions to Reduce Delay Time

Educational interventions to reduce delay time in seeking treatment
for symptoms and signs of AMI have been promising, but the studies
suffer from numerous problems making the reported results difficult
to interpret.  Most of the interventions have not tailored
interventions to characteristics of those more likely to delay
seeking treatment.  Most of the studies have limited internal
validity because they used pre-to-post intervention measurement with
no control or comparison group, making the magnitude and significance
of impact from the intervention difficult to determine.  In addition,
most of the studies were conducted in countries other than the U.S
where there are quite different health-care systems, so that
applicability to the health-care situation in the U.S. is
questionable.

A campaign in Nottingham, Britain was conducted to encourage early
reporting in over 13,000 men and women age 40 registered with three
general medical practices.  Patients from the intervention practices
reported chest pain earlier than patients in 10 comparison practices.
There was, however, a lower percentage of definite and probable AMIs
among the calls received by the "Heartwatch" line than calls received
by the patients' own doctors, implying that patients responded to the
advice to call early, but were more likely to call their own
physician than the special number (Rowley et al. 1982).

A radio and television campaign in Canada was associated with a
higher percentage of patients presenting to the ED within two hours
after onset of symptoms.  Delay time for men decreased during and
after the campaign, but for women increased (Mitic & Perkins, 1984).
There was no comparison community.

A public education campaign in Sweden used mass media to instruct the
general population and patients to dial 90,000 to call for an
ambulance for chest pain longer than 15 minutes (Herlitz et al. 1989,
1991).  For patients with confirmed AMI, median delay time was
reduced from 3 hours to 2 hours-20 minutes, and the distribution of
delay times shifted significantly downward.  The percentage of AMI
patients who received thrombolysis increased, and the estimated
infarct size was reduced significantly, but mortality was not
affected (Blohm et al., 1992).  There was no comparison community.

An educational program in Australia resulted in the percentage of
patients admitted to a coronary care unit within four hours of the
symptom onset increasing from 40-50 percent in the mid-1970s to about
55 percent after a public education media campaign (O'Rourke et al.
1989).  The effects dwindled after the campaign was discontinued.
There was no comparison community.

A public education program in King County, Washington reported a
reduction in median time from symptom onset to ED arrival from 2.6
hours to 2.3 hours, with no change in the number of patients who
arrived within 2 hours and a slight decline in those who arrived from
two to six hours after the onset of symptoms (Ho et al. 1989).  There
was a significant increase in the proportion of patients who heard
new information on AMI following the campaign, but no change in the
rate of EMS use.  There was no comparison community.

In a community-wide media campaign on delay times for suspected AMI
in the Heidelberg, Germany area, the rate of hospital admission
within four hours of symptom onset rose from 48 to 81 percent, and
the median delay was reduced from 4 hours to 3.2 hours (Rustige et
al. 1990).

Moses et al. (1991) found that a two-year public education campaign
in Jacksonville, Illinois resulted in a statistically nonsignificant
increase in the number of ED visits during the three-year study and
no change in time from onset of symptoms to ED arrival.  There was no
comparison community.

Currently, Eisenberg et al. in King County, Washington are
investigating the effect of mass media and household mailings to
residents over 50 years of age and targeted interventions to
high-risk patients.  The attempt is to reduce the time between
symptom onset and presentation to the ED and to increase the
percentage of individuals calling 911.  The interventions began in
December 1991 and will proceed for 12 months.  The project will
monitor all ED visits for chest pain, all admissions to the coronary
care units in the 16 area hospitals, and all 911 calls for complaints
of chest pain (Eisenberg, personal communication).

One study examined the effect of public education programs on
ambulance and ED utilization for individuals presenting to the ED
with chest pain.  There was a marked increase in the number of
patients with chest pain arriving at the ED during the first week of
the campaign, with the greatest increase in patients with chest pain
in whom AMI was not suspected; the number of these patients decreased
after the first week (Herlitz et al. 1991).  The effects of public
education campaigns on use of the EMS or ED, however, remains
unanswered.

Identified Need

Because of the importance of early treatment of evolving AMIs in
order to reduce morbidity and mortality, the evidence that many
people experiencing AMI symptoms often delay seeking treatment for a
variety of reasons, and the paucity of controlled studies of methods
to decrease the delay time between symptoms and seeking medical care,
the NHLBI has identified a need for further research in this area.
In addition, examination of the impact of educational campaigns on
the use of EMS and EDs is needed.  Intervention approaches targeting
community populations need to be developed based on scientific
rationales and to be evaluated using scientific methodology to
determine their effectiveness and impact.

Objectives and Scope

The objective of this program is to develop and evaluate the
effectiveness and impact of community-based education to reduce delay
time for symptoms and signs of AMI.  The focus is on decreasing the
delay between symptom onset and contact with the health-care system
by decreasing delay time associated with patient recognition and
action.

To address the objective of this program, the proposed research
should include, at a minimum, three components:  (1) a
community-based educational intervention that has the goal of
decreasing delay time associated with patient recognition and action,
(2) a study design utilizing control or comparison communities to
enhance internal validity, and (3) measurement of delay time from AMI
symptom onset to contact with the health-care system (for example,
arrival at the hospital ED).  Details of the intervention, study
design, and measurement are in the hands of the investigators.

One strategy of collaborative research to address the objective of
this RFA is outlined.  Applicants may propose other strategies and
awardees may collaboratively develop a study protocol with different
study design, intervention, and/or measurement than is described in
this RFA, as long as the purpose of the RFA is met.  To assure that
there is at least one mutually acceptable strategy that the
collaborative group deems worthy of development into a final
protocol, each applicant is asked to address the research strategy
cited in this RFA.  However, applicants are free to propose
additional or alternate strategies to be considered.

Participating institutions will collaborate to develop and then
follow a uniform study protocol with standardized study design, data
collection procedures, and intervention approaches.  The
collaborative protocol will be developed during the first year of the
study by the Steering Committee of the study, which will be composed
of the awardees and the NHLBI Project Scientist.  The protocol will
be subject to peer review by an uninvolved expert group.  The study
will proceed into its implementation phase only with the concurrence
of the awardees and the NHLBI.

The strategy of collaborative research is envisioned to be a
multicenter controlled community trial where the community is the
unit of assignment and of analysis.  This could be accomplished by
each Field Site studying one or more pair(s) of communities matched
on demographic and other characteristics, with one of each pair
randomly assigned to intervention and one to control condition.  The
intervention is envisioned as a multifactorial, community-based
educational intervention.  The primary measure of impact is
anticipated to be change in delay time from symptom onset to arrival
at the hospital ED, using a clinically meaningful measure of delay
time such as median delay time or proportion of patients seen within
a certain specified time frame after symptom onset.  Other measures
of the impact on the EMS and ED systems also are expected to be
evaluated; examples include the use of the EMS system for symptoms of
an AMI, use of the ED for cardiac and noncardiac chest pain, delivery
of thrombolytic therapy, and mortality.

Because of the early stage of research in this area, data are not
available to estimate with accuracy the sample size of communities
for a community trial of educational interventions on delay time.
However, NHLBI estimates that 16 to 20 study communities (8 to 10
intervention communities, each with a matched comparison community)
probably would provide reasonable power to detect differences in
delay time that are clinically meaningful and that are possible based
on the intervention literature to date.  This size study would
require 4 to 8 Field Sites, depending on the number of communities
per Field Site, and one Coordinating Center.

Additional Factors To Consider in the Application

This section contains information to help in the development of
applications and is not intended to represent requirements for
funding.  Consideration of these issues, however, should help
strengthen applications.

Applications will be strengthened by describing the available
communities from which the study communities can be selected,
including demographics, hospitals and their catchment areas, EMS
services, community organizations, and other characteristics that are
relevant to interventions and measurements being proposed.  Baseline
data collected during the first year of the study, including data on
baseline delay times, may be proposed as a selection criterion for
the study communities.  Alternately, specific study communities may
be proposed at the outset.  If more than one pair of study
communities is proposed, the pairs should be independent of each
other, for example by sufficient geographic separation, in order to
meet statistical assumptions for independence needed for analysis of
a community trial.  Communities within each pair should be selected
to avoid contamination of intervention and measurement, for example
by assuring that the intervention program will be restricted to the
intervention community and that the EMS system and hospital ED
catchment areas do not overlap.

The size of each community should be adequate to provide enough
events of interest.  An estimated 300 to 500 events (i.e., cases of
"rule-out AMI") in each community should provide reasonable estimates
of delay time; this would most likely require a population of 50,000
or more.  Communities should have one or more hospital and an EMS
system from which to obtain data.  To assure comparability of
communities with respect to availability of EMS services, the 911
emergency phone system should be in place at the time of application.

Communities could be selected by a variety of different approaches.
For example, a two-county area could be designated as one community
so that rural populations with sparse populations could be included.
Communities within a metropolitan area could be proposed, but
evidence that they are distinct and do not overlap would help assure
reviewers that intervention and measurement contamination will not
occur.  Selection of ethnically diverse communities for study is
encouraged.  Letters of support from community organizations, EMS
systems, media, and other entities proposed to be involved in
intervention and/or measurement will be helpful in determining the
feasibility of conducting the study in the proposed communities.

The study design is envisioned as a multicenter community trial with
community as the unit of assignment and analysis.  An example of how
this design could be implemented is for each Field Site to propose
one or more pair(s) of communities, matched on demographic and other
characteristics related to the outcome measure of interest (i.e.,
delay time), and for one community of each pair to be assigned
randomly to intervention or control group.  Measures of delay time at
baseline, during, and post-intervention in the intervention and
comparison communities would be compared by statistical methods to
determine the impact of the intervention.  More than one baseline
measure of delay time may be a possible means to increase the
accuracy of delay time measurement and increase the power of the
study.

Because changing behaviors is a complex task, multifactorial
intervention programs based on sound behavior theory are likely to be
more effective.  The intervention is envisioned as a community-based,
multifactorial intervention program involving several components:
(1) public information and persuasive communication, (2) patient
education, (3) community organization, and (4) professional
education.  Descriptions of interrelationships and coordination
between proposed intervention components will be helpful in assessing
how the intervention components will be combined into an overall
intervention program.

Training health-care professionals in diagnostic and treatment
procedures for patients presenting with AMI symptoms is out of the
scope of this research.  Education directed toward health
professionals to encourage patients to contact directly the EMS and
to use EDs because of the importance of time in seeking care could be
considered within the scope of the program.  Applicants should be
aware that the National Heart Attack Alert Program is planning to
develop and nationally disseminate educational materials for patients
with diagnosed CHD to be delivered in health-care settings.

Process evaluation can be used to determine the extent to which the
intervention is implemented as designed and the extent to which
messages reach the target audience.  Process evaluation can also
provide information about the comparison communities that could help
identify unanticipated events (historical or secular) that may have
an impact on the factors of interest.

Data collection and analysis plans for the outcome variables of the
study should be described, including delay time, which is anticipated
to be time from symptom onset to arrival at the ED.  The specific
measure of delay time to be used as the primary study outcome measure
will be determined during protocol development, but the measure
should be clinically meaningful; examples to consider include median
delay time, proportion of cases with delay time shorter than a
specified time (e.g., one hour, 2 hours, 4 hours, 6 hours), or a
downward shift in the delay time frequency distribution.  The source
of data for delay time should be specified (e.g., patient interviews,
EMS records, ED records), and any sampling scheme should be
described.  If multiple hospitals or EMS systems serve the same
community, any scheme to sample hospitals, EDs, or EMS systems should
be described and justified.

A cost analysis plan to measure the costs of both intervention and
any increased use of EMS and ED systems by individuals seeking
treatment in response to symptoms and signs of AMI also could be
proposed.

Applications for the Coordinating Center should address statistical
and design issues relevant to community studies, including, for
example, the appropriate unit of analysis, power and sample size,
methods of assignment to treatment condition, minimization of bias,
and other issues deemed important by the applicant.

Timetable

The proposed research should be in the form of four-year
Demonstration and Education Projects.  In the first year, the
collaborative study protocol will be developed and baseline data will
be collected.  In the second and third years, the protocol will be
implemented and process and impact measurements will be taken.  In
the fourth year, measurement and data collection will be completed,
data will be analyzed, and manuscripts written.

SPECIAL REQUIREMENTS

To promote the development of a collaborative program among the award
recipients, a number of minimum issues need to be addressed in the
applications.  Applicants should discuss the rationale for their
choice of intervention approaches and data measurement, document
their ability to develop and implement community-based interventions,
describe their ability to interact effectively with other Field Sites
and the Coordinating Center, discuss their capability to participate
in collaborative meetings and conference calls, and state their
willingness to follow the common protocol that will be agreed upon
during the first year of the study.

In addition to the Field Site awards, a separate award will be made
for a Coordinating Center.  The Coordinating Center will have as its
major responsibilities participating in planning for data collection,
instrument development, and collecting, editing, storing, and
analyzing data generated by the Field Sites.  It will provide a
detailed report of accumulating data and project performance at
six-month intervals and a final report.

The study organization is described under Terms and Conditions,
below.

Terms and Conditions of Award

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 92, and other HHS,
PHS, and NIH Grant Administration policy statements.

The administrative and funding instrument used for this program is a
cooperative agreement (U01), an "assistance" mechanism (rather than
an "acquisition" mechanism) in which substantial NIH scientific
and/or programmatic involvement with the awardee is anticipated
during performance of this activity.  Under the cooperative
agreement, the NIH purpose is to support and/or stimulate the
recipient's activity by collaborating and otherwise working jointly
with the award recipient in a partner role, but it is not to assume
direction, prime responsibility, or a dominant role in the activity.
Consistent with this concept, awardees have the prime responsibility
for the project as a whole, although some tasks and activities are to
be shared among the awardees and the NHLBI Project Scientist, as
described below.

Awardees will have the usual responsibilities of assistance award
recipients, including protocol development, participant recruitment
and follow-up, data collection, quality control, interim data and
safety monitoring, final data analysis and interpretation, and
preparation of publications, as well as responsibilities for
collaboration with other awardees and with the NHLBI Project
Scientist.

The NHLBI Project Scientist (Medical Officer, Prevention and
Demonstration Branch, Division of Epidemiology and Clinical
Applications), in addition to the usual stewardship responsibilities,
will have responsibilities in protocol development, quality control,
interim data and safety monitoring, final data analysis and
interpretation, preparation of publications, collaboration with
awardees, and project coordination.

It is anticipated that awardees will have lead responsibilities in
all joint tasks and activities, except it is anticipated that the
NHLBI Project Scientist will have lead responsibilities in quality
control and catalyzing the interim monitoring of data and safety, and
may, consistent with publication policy to be adopted by the Steering
Committee, have lead responsibilities in the preparation of some
publications.

A Steering Committee, composed of the Principal Investigator(s) of
each Clinical Group, the Principal Investigator(s) of the
Coordinating Center, and the NHLBI Project Scientist will be the main
governing board of the study and will have primary responsibility for
developing common protocols, facilitating the conduct and monitoring
of studies, and reporting study results.  Each Field Site, the
Coordinating Center, and the NHLBI Project Scientist will have one
vote.  The chairperson, who will be someone other than an NHLBI staff
member, will be selected by the Steering Committee. Subcommittees
will be established by the Steering Committee, as it deems
appropriate; the NHLBI will be represented on subcommittees as deemed
appropriate by the NHLBI Project Scientist.

The collaborative protocols will be developed by the Steering
Committee.  Data will be submitted centrally to the Coordinating
Center.  Protocols will define rules regarding access to data and
publications.  An independent Data and Safety Monitoring Board, to be
appointed by the NHLBI, will review progress at least annually and
report to the NHLBI.

Awardees will retain custody of and have primary rights to the data
developed under these awards, subject to Government rights of access
consistent with current HHS, PHS, and NIH policies.

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

Any disagreement that may arise on 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 selected
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.

STUDY POPULATIONS

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

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

The composition of the proposed study population must be described in
terms of gender and racial/ethnic group.  In addition, gender and
racial/ethnic issues must be addressed in developing a research
design and sample size appropriate for the scientific objectives of
the study.  This information must be included in the form PHS 398
(rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in
Section 5, Human Subjects.  Applicants are urged to assess carefully
the feasibility of including the broadest possible representation of
minority groups.  However, NIH recognizes that it may not be feasible
or appropriate in all research projects to include representation of
the full United States racial/ethnic minority populations (i.e.,
Native Americans, Asian/Pacific Islanders, Blacks, Hispanics).

The rationale for studies on single minority population groups should
be provided.

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

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

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

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

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

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

LETTER OF INTENT

Prospective applicants are asked to submit, by October 12, 1993, 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 the RFA in response to
which the application may be submitted.

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 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 sent to Dr. C. James Scheirer at the
address listed under INQUIRIES.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research; from the Office of
Grants Inquiries, Division of Research Grants, National Institutes of
Health, 5333 Westbard Avenue, Room 449, Bethesda, MD  20892,
telephone 301/435-0714; and from the NIH program administrator named
below.

The RFA label available in the PHS 398 (rev. 9/91) 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, the RFA title and number must be typed on
line 2a of the face page of the application form and the YES box must
be marked.

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

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

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

C. James Scheirer, Ph.D.
Review Branch, Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Westwood Building, Room 548
Bethesda, MD  20892
Telephone:  (301) 594-7452

It is important to send these two copies at the same time as the
original and that three 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 December 21, 1993.  If an
application is received after that date, it will be returned to the
applicant without review.  The Division of Research Grants (DRG) will
not accept any application in response to this announcement that is
essentially the same as one currently pending initial review, unless
the applicant withdraws the pending application.  The DRG will not
accept any application that is essentially the same as one already
reviewed.  This does not prelude the submission of substantial
revisions of applications already reviewed, but such applications
must include an introduction addressing the previous critique.

Awards for a Field Center and Coordinating Center under this RFA will
not be made to the same Principal Investigator (PI) or team of
investigators.  The same institution may apply for both a Field Site
and the Coordinating Center award, but the applications for each must
be from different individuals and must be submitted separately.

REVIEW CONSIDERATIONS

General Considerations

All applicants will be judged on the basis of the scientific merit of
their proposed protocols and their documented ability to conduct the
essential study components as broadly outlined in the RESEARCH
OBJECTIVES of the RFA.  Although the technical merit of the protocol
is important, it will not be the sole criterion for selection of an
application.  Other considerations such as the importance and
timeliness of the proposed study, access to study subjects, and
multidisciplinary nature of the studies will be part of the
evaluation criteria.

Review Method

Upon receipt, applications will be reviewed for the completeness by
DRG and responsiveness by the NHLBI.  Incomplete applications will be
returned to the applicant without further consideration.  If the
application is not responsive to the RFA, NHLBI staff will contact
the applicant to determine whether to return the application to the
applicant or submit it for review in competition with unsolicited
applications at the next review cycle.

Applications may be triaged by an NHLBI peer review group on the
basis of relative competitiveness.  The NIH will withdraw from
further competition those applications judged to be non-competitive
for award and notify the applicant Principal Investigator and
institutional official.  Those applications judged to competitive
will undergo further scientific merit review.  Those applications
that are complete and responsive will be evaluated in accordance with
the criteria stated below for scientific/technical merit by an
appropriate peer review group convened by the NHLBI.  The second
level of review will be provided by the National Heart, Lung and
Blood Advisory Council.

Review Criteria

Applicants are encouraged to submit and describe their own ideas on
how best to meet the goals of the proposed research in their specific
protocols, and they are expected to address issues identified under
SPECIAL REQUIREMENTS in the Request for Applications.  Applications
will be judged primarily on the scientific quality of the
application, the appropriateness, importance and timeliness of the
proposed study, adequacy of facilities, access to study subjects, the
multidisciplinary nature of the study, the approach to cost
containment, the discussion of considerations relevant to this RFA,
the 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 Project Scientist.

The review group will assess the scientific merit of the protocols
and related factors, including:

Field Sites

o  scientific, technical, and medical significance and originality of
proposed research;

o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research, including
intervention, measurement, and evaluation methodology;

o  understanding of the scientific, statistical, logistical, and
technical issues underlying a multicenter collaborative study;

o  understanding issues related to measurement of delay time,
measurement of use of EMS and EDs, process and impact evaluation of
intervention implementation, and study design and sample size issues
for a multi-community study with community as the unit of assignment
and analysis;

o  qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of the proposed research;

o  availability of the resources necessary to perform the research,
including availability of communities and willingness to participate
by relevant community organizations;

o  administrative, supervisory, and collaborative arrangements for
achieving the goals of the program, including willingness to
cooperate with other participating Field Sites, the Coordinating
Center, and the NHLBI;

o  appropriateness of the proposed budget in relation to the proposed
research.

Coordinating Center

o  understanding of the scientific, statistical, logistical, and
technical issues underlying multicenter collaborative studies,
including sample size considerations for a multi-community study with
community as the unit of assignment and analysis, and data analysis
plans;

o  understanding of the statistical, logistical, and technical issues
of measurement of delay time, measurement of use of EMS and EDs,
process evaluation of intervention implementation, and evaluation of
the impact of the intervention;

o  ability to take a leadership role in the areas of study design,
statistics, logistics, data acquisition and management, quality
control, and data analysis;

o  adequacy of the proposed plans for acquisition, transfer,
management, and analysis of data, quality control of data collection
and of intervention implementation, and overall coordination of study
activities;

o  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 the effective coordination of the multicenter
study;

o  administrative, supervisory, and collaborative arrangements for
achieving the goals of the program, including willingness to
cooperate with the participating Field Sites and the NHLBI;

o  facilities, equipment, and organizational structure to assist
effectively the Field Sites in implementing the study including
delivering the intervention and conducting data collection
procedures, and for overall coordination of study activities;

o  appropriateness of the proposed budget in relation to the proposed
research.

AWARD CRITERIA

Applications recommended by the NHLBI Advisory Council will be
considered for award based upon (a) scientific and technical merit,
including the requirements explicitly stated in the RFA; (b) program
balance, including sufficient compatibility of features to make a
successful collaborative program a reasonable likelihood and
representation of minority communities; and (c) availability of
funds.

Letter of Intent Receipt Date:     October 12, 1993
Application Receipt Date:          December 21, 1993
Review by NHLBI Advisory Council:  May 26-27, 1994
Anticipated Award Date:            July 1, 1994

INQUIRIES

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

Direct inquiries regarding scientific issues to the Project
Scientist:

Denise Simons-Morton, M.D., M.P.H., Ph.D.
Division of Epidemiology and Clinical Applications
National Heart, Lung, and Blood Institute
Federal Building, Room 604
7550 Wisconsin Avenue
Bethesda, MD  20892
Telephone:  (301) 496-3503

Direct inquiries regarding review and application procedures and
address the letter of intent to:

C. James Scheirer, Ph.D.
Review Branch, Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Westwood Building, Room 548
Bethesda, MD  20892
Telephone:  (301) 594-7452
FAX:  (301) 594-7407

Direct inquiries regarding fiscal and administrative matters to:

Mr. William W. Darby
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Westwood Building, Room 4A11C
Bethesda, MD  20892
Telephone:  (301) 594-7458
FAX:  (301) 594-7492

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.837.  Awards are made under authorization of the
Public Health Service Act, Title IV, Part A (Public Law 78-410, as
amended by Public Law 99-158, 42 USC 241 and 285) and administered
under PHS grants policies and Federal Regulations 42 CFR 52 and 45
CFR Part 74 and 92.  This program is not subject to the
intergovernmental review requirements of Executive Order 12372 of
Health Systems Agency review.

REFERENCES

American College of Cardiology/American Heart Association (ACC/AHA)
Subcommittee.  Guidelines for the early management of patients with
acute myocardial infarction.  J Am Coll Cardiol 1990;16:249.

Alonzo AA.  The impact of the family and lay others on care-seeking
during life-threatening episodes of suspected coronary artery
disease.  Soc Sci Med 1986;22:1297-1311.

Blohm M, Herlitz J, Hartford M, et al.  Consequences of a media
campaign focusing on delay in acute myocardial infarction.  Am J
Cardiol 1992;69:411-413.

Braunwald E.  Myocardial reperfusion, limitation of infarct size,
reduction of left ventricular dysfunction and improved survival.
Circulation 1989;79:441-444.

Califf RM, Topol EJ, Gersh BJ.  From myocardial salvage to patient
salvage in acute myocardial infarction:  The role of reperfusion
therapy.  J Am Coll Cardiol  1989;14:1382-1388.

Clark LT, Bellam SV, Shah AH, Feldman JG.  Analysis of prehospital
delay among inner-city patients with symptoms of myocardial
infarction: Implications for therapeutic intervention.  J Natl Med
Assoc 1992;84:931-937.

Cooper RS, Simmons B, Castaner A, et al.  Survival rates and
pre-hospital delay during myocardial infarction among black persons.
Am J Cardiol 1986;57:208-211.

Dracup K, Moser DK.  Treatment-seeking behavior among those with
symptoms and signs of acute myocardial infarction.  In: LaRosa JH,
Horan MJ, Passamani ER, (eds.)  Proceedings of the National Heart,
Lung, and Blood Symposium on Rapid Identification and Treatment of
Acute Myocardial Infarction.  U.S. Department of Health and Human
Services, Public Health Service, National Institutes of Health,
National Heart, Lung, and Blood Institute, September 1991;25-45.

Gilchrist IC.  Patient delay before treatment of myocardial
infarction.  Br Med J  1973;1:535-537.

Goldberg RJ, Gurwitz J, Yarzebski J, Landon J, Gore JM, Alpert JS,
Dalen PM, Dalen JE.  Patient delay and receipt of thrombolytic
therapy among patients with acute myocardial infarction from a
community-wide perspective.  Am J Cardiol  1992;70:421-425.

Grines CL, DeMaria AN.  Optimal utilization of thrombolytic therapy
for acute myocardial infarction:  Concepts and controversies.  J Am
Coll Cardiol 1990;16:223-231.

Gruppo Italiano per lo Studio della Stretochinasi nell'Infarto
Miocardico (GISSI).  Effectiveness of intravenous thrombolytic
treatment in acute myocardial infarction.  Lancet 1986:I:397-401.

Gillum RF, Feinlab M, Margolis JR, Fabsitz RR, Brasch RC.  Delay in
the prehospital phase of acute myocardial infarction.  Arch Intern
Med 1976;136:649-654.

Hackett TP, Cassem NH.  Factors contributing to delay in responding
to the signs and symptoms of acute myocardial infarction.  Am J
Cardiol  1969;24: 651-658.

Herlitz J, Blohm M, Hartford M, et al.  Delay time in suspected acute
myocardial infarction and the importance of its modification.  Clin
Cardiol 1989;12(7):370-374.

Herlitz J, Hartford M, Karlson BV, et al.  Effect of a Media Campaign
to Reduce Delay Times for Acute Myocardial Infarction on the Burden
of Chest Pain Patients in the Emergency Department.  Cardiology
1991;79:127-134.

Ho MT, Eisenberg MS, Litwin PE, et al.  Delay between onset of chest
pain and seeking medical care:  The effect of public education.  Ann
Emerg Med 1989;18:727-731.

Hofgren K, Bondestam D, Johansson FG, et al.  Initial pain course and
delay to hospital admission in relation to myocardial infarction
size.  Heart Lung 1988;17:274-280.

Koren G, Weiss AT, Hasin Y, Appelbaum D, et al.  Prevention of
myocardial damage in acute myocardial ischemia by early treatment
with intravenous streptokinase.  N Engl J Med 1985;313:1384-1389.

Leitch JW, Birbara T, Freedman B, Wilcox I, Harris PJ.  Factors
influencing the time from onset of chest pain to arrival at the
hospital.  Med J Aust 1989;150:6-8.

Matthews KA, Siegel JM, Kuller LH, et al.  Determinants of decisions
to seek medical treatment by patients with acute myocardial
infarction symptoms.  J Person Soc Psych  1983;44:1144-1156.

Maynard C, Althouse R, Olsufka M, et al.  Early versus late hospital
arrival for acute myocardial infarction in the Western Washington
thrombolytic therapy trials.  Am J Cardiol  1989;63:1296-1300.

Mitic WR, Perkins J.  The effect of a media campaign on heart attack
delay and decision times.  Can J Public Health  1984;75:414-418.

Moses HW, Engelking N, Taylor GJ, et al.  Effect of a two-year public
education campaign on reducing response time of patients with
symptoms of acute myocardial infarction.  Am J Cardiol
1991;68:249-251.

Moss AJ, Goldstein S.  The pre-hospital phase of acute myocardial
infarction.  Circulation  1970;41:737-742.

Moss AJ, Wynar B, Goldstein S.  Delay in hospitalization during the
acute coronary period.  Am J Cardiol  1969;24:659-665.

LaRosa JH, Horan MJ, Passamani ER (eds.)  Proceedings of the National
Heart, Lung, and Blood Institute Symposium on Rapid Identification
and Treatment of Acute Myocardial Infarction.  U.S. Department of
Health and Human Services, U.S. Public Health Service, National
Heart, Lung, and Blood Institute (NHLBI), 1991.

National Heart, Lung, and Blood Institute (NHLBI).  Morbidity and
Mortality Chartbook on Cardiovascular, Lung, and Blood Diseases.
U.S. Department of Health and Human Services, U.S. Public Health
Service, 1992.

O'Rourke, Thompson PL, Ballantyne K. Community aspects of coronary
thrombolysis:  Public education and cost effectiveness.  In: Julian
DG, Kubler W, Norris RM, Swan HJ, Collen D, Verstraete M, eds.
Thrombolysis in Cardiovascular Disease.  New York:  Marcel Dekker,
1989;309-324.

Rawles JM, Haites NE.  Patient and general practitioner delays in
acute myocardial infarction.  Br Med J  1988;296:882-4.

Rowley JM, Hill JD, Hampton JR, Mitchell JRA.  Early reporting of
myocardial infarction:  Impact of an experiment in patient education.
Br Med J  1982;1:1741-1746.

Rustige JM, Burczyk U, Schiele R, Werner A, Senges J.  Media campaign
on delay times in suspected myocardial infarction--the Ludwigshafen
Community Project [Abstract].  Eur Heart J 1990;11 (suppl):171.

Schmidt SB, Borsch MA.  Multivariate analysis of pre-hospital delay
during acute myocardial infarction in the thrombolytic era.
Circulation  1989;80 (Suppl II):II-637.

Schroeder JS, Lamb IH, Hu M.  The pre-hospital course of patients
with chest pain:  Analysis of the prodromal, symptomatic,
decision-making, transportation and emergency room periods.  Am J Med
1978;64:742-748.

Second International Study of Infarct Survival (ISIS-2) Steering
Committee. Intravenous streptokinase given within 0-4 hours of onset
of myocardial infarction reduced mortality in ISIS-2.  Lancet
1987;I:502.

Simon AB, Feinlab M, Thompson HK.  Components of delay in the
pre-hospital phase of acute myocardial infarction.  Am J Cardiol
1972;30:476-482.

Turi ZG, Stone PH, Muller JE, et al.  Implications for acute
intervention related to time of hospital arrival in acute myocardial
infarction.  Am J Cardiol  1986;58:203-209.

Wielgosz ATJ, Nolan RP, Earp JA, et al.  Reasons for patients' delay
in response to symptoms of acute myocardial infarction.  Can Med
Assoc J 1988;139:853-857.

World Health Organization (WHO).  World Health Stat Q 1988;41:(3/4).

Yusuf S, Collins R, Peto R, et al.  Intravenous and intracoronary
fibrinolytic therapy in acute myocardial infarction:  Overview of
results on mortality, reinfarction, and side effects from 33
randomized controlled trials.  Euro Heart J  1985;6:556-585.

.

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