RELEASE DATE:  April 28, 2004                

RFA NUMBER:   RFA-HL-04-023            

EXPIRATION DATE: October 23, 2004

Department of Health and Human Services (DHHS)

National Institutes of Health (NIH)

National Heart, Lung, and Blood Institute (NHLBI) 




o Purpose of this RFA            
o Research Objectives
o Mechanism of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Technical Assistance Workshops
o Letter of Intent
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citation


The National Heart, Lung, and Blood Institute (NHLBI) invites applications for 
cooperative agreements to conduct five-year studies in American Indian/Alaskan 
Native (AI/AN) populations to test the effectiveness of behavioral interventions to 
promote the adoption of healthy lifestyles and/or improve behaviors related to 
cardiovascular (CV) risk, such as weight reduction, regular physical activity, and 
smoking cessation.  These behaviors and lifestyles are known to affect biological 
cardiovascular risk factors, such as hypertension, dyslipidemia, obesity, glucose 
intolerance, and diabetes.  A central feature of this project is to develop and test 
culturally appropriate interventions that could be incorporated into clinical 
programs of the community health care systems or delivered through public-health 
approaches in Native communities.  The interventions tested should be sustainable 
and capable of being disseminated to other Native communities after termination of 
research support.  

The concept for this RFA was developed in consultation with AI/AN Tribes, 
recognizing the government-to-government relationship between AI/AN Tribes and the 
United States, and incorporates recommendations of a working group of AI/AN health 
experts.  The long-term goal of this RFA is to reduce cardiovascular disease 
mortality and morbidity in AI/AN.  This initiative focuses on primary and primordial 
prevention, important approaches that can contribute to that goal. 


A. Background

1. Burden of Disease in AI/AN Communities. Observational studies have shown that 
many AI/AN communities bear a heavy burden of cardiovascular disease (CVD) and 
cardiovascular risk factors (e.g., obesity, diabetes) that could be reduced through 
effective interventions on modifiable risk factors.  The high burden of disease will 
worsen unless behaviors and lifestyles affecting CVD risk can be changed.  
Widespread concern exists among AI/AN communities and health organizations that 
despite extensive documentation of these problems in observational studies, few 
intervention studies have been launched to test effective solutions in their 
environment.  Tribal leaders and AI/AN working group members have urged that health 
research in their communities focus on the most serious health issues they face, and 
they have identified CVD, obesity, and diabetes, as being among these issues.

Prevalence of obesity in AI/AN communities is about 50% higher than in the U.S. 
general population--in which obesity is often described as being of epidemic 
proportions.  In some AI/AN communities, cigarette smoking, sedentary lifestyle, and 
stress augment the adverse effects of obesity.  AI/AN are particularly vulnerable to 
Type II diabetes, a problem exacerbated by high rates of obesity.  Diabetes 
prevalence is 3-20 fold higher among AI/AN than in the general U.S. population.  It 
is an important cause of coronary heart disease, cardiomyopathy end-stage renal 
disease, non-traumatic amputation, and vision impairment.  Lipid abnormalities also 
are common in Type II diabetics, particularly high triglycerides and low HDL-
cholesterol levels.  Dyslipidemia and blood pressure can be improved by appropriate 
changes in diet and by increased exercise.  CVD risk is also substantially improved 
by smoking cessation.  In addition, attention to high stress levels, sleep loss, and 
depression may be warranted because of evidence that they may influence the health 
behaviors of interest in this RFA.  For example, poorer diet, higher smoking rates, 
and physical inactivity are more prominent in those with high stress, sleep 
disorders, or depression.  These psychosocial factors also are associated with CVD 
progression in observational epidemiologic studies, and there is evidence from 
smaller clinical studies they may affect mechanisms leading to CVD.  The purpose of 
this RFA, however, is not to focus on these factors, but only to address them if 
they affect the targeted behaviors in the population of interest.

2. Need for Community Involvement.  An important consideration of working with AI/AN 
communities is that interventions should be developed with direct community 
involvement and in a way that approaches proven to be beneficial are sustainable 
after the study is completed (Department of Health and Human Services. Consultation 
with American Indians and Alaska Natives. A report on the continuing dialogue 
between the Department of Health and Human Services and American Indian and Alaska 
Native leaders.  January 2001).  NHLBI convened an AI/AN Intervention Working Group 
that included representatives from each Indian Health Service  Area, and from major 
AI/AN organizations.  The Working Group recommended community involvement from the 
initiation of planning, with Tribal consultation as the initial step.  Based on 
these recommendations, NHLBI consulted elected representatives of AI/AN communities 
during the development of this initiative and also participated in discussions with 
AI/AN health professionals.  The consultation process identified several diseases 
that are within the mission of NHLBI, including CVD and many of its risk factors–
high blood pressure, diabetes, and obesity, as well as many behaviors and lifestyles 
that affect CVD risk, such as diet high in saturated fat and salt, lack of physical 
activity, and cigarette smoking--as major public health threats that are common to 
many of these communities.  The consultation process also recommended aggressive CVD 
risk factor management as a viable and sustainable intervention strategy, and 
identified interventions for the above CVD risk factors.  The consultation results 
were reviewed with the AI/AN Intervention Working Group, which made recommendations 
to the NHLBI on some parameters for this initiative.  (The minutes of the three 
Working Group meetings are available at the following web site:

Reducing significant and worsening health issues among AI/AN communities and 
individuals may be fostered by greater understanding of how to enhance their 
strengths and resiliencies.  Although American Indian communities have relied on 
health research and medical science to reduce health disparities, they also have 
relied on their own medical, psychological, organizational, and cultural assets and 
strengths to survive major harms and disruptions over the centuries, and to rebound 
from insults to health. (For research about resiliencies, see  This RFA attempts to 
harness the synergy that can come from the interaction of these two important 
contributors to health in AI/AN communities by promoting active and substantial 
participation by the community in the development, implementation, and dissemination 
of intervention research. 

B. Objectives and Scope

1. Research Questions. The purpose of this initiative is to test the effectiveness 
of behavioral interventions to promote the adoption of healthy lifestyles and/or 
adoption of behaviors related to CVD risk, such as healthy diet, regular physical 
activity, and smoking cessation that are known to affect biological cardiovascular 
risk factors, such as hypertension, dyslipidemia, obesity, glucose intolerance, and 
diabetes.  The primary research question to be addressed in these studies is: Can a 
culturally appropriate behavior change program in AI/AN participants lead to 
sustained favorable changes in health behaviors and lifestyles, which are known to 
improve CVD risk factors?  The research plan should be developed consistent with 
community attitudes and readiness for change. The intervention program should be 
designed so that it could be sustained within the entire community within existing 
resources, and, if successful, disseminated elsewhere. 

2. Eligibility.  The target population is adult and/or children AI/AN at high risk 
for CVD, but free of clinical (or previously diagnosed) CVD.   Each applicant should 
provide his or her own definition of “high risk” and criteria for ascertainment of 
whether or not potential participants have CVD.  Applicants may propose a primary 
prevention program, that is, improving CVD risk factor(s) in those who possess a 
risk factor (e.g., already obese or hypertensive), and/or a primordial prevention 
program, that is, preventing the occurrence of the risk factor (e.g., preventing 
obesity or hypertension).  Although the interventions tested must be directed toward 
behaviors, CVD risk factors used to identify eligibility may be either behavioral or 
biological.  Examples of potential eligibility criteria include smoking, obesity, 
sedentary lifestyle, glucose intolerance, diabetes, hypertension, dyslipidemia.  
Applicants should propose objective measures for eligibility, and identify 
eligibility criteria and provide support for their choices in terms of the 
availability of the target population, the prevalence of the condition(s), and 
suitability for the proposed intervention. 

3.  Design.  Applicants should propose either an experimental design with either an 
individually or family randomized design, or alternatively, a quasi-experimental 
design with community or school randomization.  Applicants proposing a group- or 
family-based study must include at least 2 schools or communities in the intensive 
intervention condition and at least 2 schools or communities in the comparison 
condition.  Applicants who propose an individually randomized study, but who propose 
to include family members or significant others in the intervention to increase 
structure and social support, should discuss how this approach may affect plans for 
informed consent, randomization procedures, data collection, and statistical 

The design should include at least two randomized groups: an intensive intervention 
group and a comparison group.  All participants should receive some benefit from 
participating in the study.  Participants enrolled in the comparison group may 
receive a less intensive intervention, such as education and advice, or an alternate 
intervention, such as injury prevention.  Participants in both the intensive 
intervention group and the comparison group will continue to receive medical care 
from their usual source of care.

Each application should identify the specific research question to be addressed, the 
intervention(s) to be delivered, the expected effects of the intervention (including 
magnitude of change), the statistical analyses to be conducted (for experimental 
designs), and, if successful, plans to disseminate the intervention.  Applicants 
should describe the characteristics of their populations and proposed sample sizes 
with supporting power calculations (for experimental designs). 

4. Interventions.  Applicants are strongly encouraged to propose intervention 
designs that are of maximum duration within the time limits and budget of this 
initiative.   We envision that interventions can be up to two years in duration 
(including any booster or maintenance intervention) because sustained behavior 
change is needed to reduce risk of disease.  Because the targeted health behaviors 
tend to cluster, applicants are strongly encouraged to propose intervention 
components targeted at two or more behaviors (e.g., dietary change and increased 
physical activity).  Targeted behaviors include: increasing regular physical 
activity, smoking cessation, reducing or preventing overweight and obesity, and 
improving diet.

Applicants may wish to consider adding specific components to their intervention 
programs to further promote self-management of CVD risk reduction.  For example, 
intervention(s) could include approaches to improve self-management of CVD risk 
factors and provide education on how to interact with health-care providers (e.g., 
health-care seeking, keeping appointments, and adhering to health-care 

The behavioral interventions to be tested will be consistent with community values 
and may include traditional health, medical, and/or cultural practices.  Examples of 
possible intervention strategies include the following or combinations of  the 
following. However, applicants are not limited to these strategies.

o adding a cultural context regarding the ceremonial use of tobacco to smoking 
cessation programs to reduce smoking;
o using traditional AI/AN games, sports, and dances to increase moderate to vigorous 
physical activity on a regular basis;
o re-introducing traditional AI/AN diets, which are low in saturated fat, to improve 
blood cholesterol;
o using traditional foods, decreasing alcohol consumption to recommended levels, and 
increasing culturally relevant physical activity to promote weight loss and weight 
o providing behavioral interventions or referral for treatment of high stress, 
depression and sleep difficulties in order to enhance the success of the behavioral 
and lifestyle interventions addressing obesity, diet, or physical activity, if 
warranted and justified as a related issue.

Environmental approaches to behavioral change may also be considered as 
interventions as they affect the targeted health behaviors. Examples include:

o modifying the commodity foods program to reduce saturated fat and increase fresh 
fruits and vegetables to improve dietary behaviors;
o increasing the availability of fresh fruits and vegetables at community stores to 
encourage their consumption.

The interventions should be delivered by individuals (e.g., behavioral 
professionals, community health workers, counselors, nutritionists, nurse 
practitioners, physician assistants, traditional healers) drawn from the community 
to the greatest extent possible.  
5. Collaboration.  The studies supported by this initiative will not use a common 
study protocol.  However, whenever possible, investigators should collaborate and 
report in a standardized manner when they are measuring key common variables, such 
as diet, blood pressure, physical activity, height and weight, and smoking status 
and rates.  Investigators may also use different methods of measuring similar 
outcome variables when justified.  Investigators may also collaborate in the 
development of formative assessment measures, such as survey instruments and focus 
group guidelines.  Investigators are encouraged to collaborate for data archiving, 
such as selecting a single archive and archiving format.  Investigators should 
indicate in their application their willingness to collaborate on the development 
and use of standardized measurement protocols, data archiving, and coordination of 
formative assessment and possibly of intervention approaches, and their willingness 
to collaborate with NHLBI scientists in all aspects of the study.

6. Outcome Measures.  Because the research objectives are to change behaviors that 
affect CVD risk, the primary outcome measures should be objective measures of the 
behaviors that the intervention targets.  In some cases these may be measures of CVD 
risk factors that the behaviors affect. Potential outcome measures include, but are 
not limited to:

o serum cotinine for smoking status;
o nutrient biomarkers as measures of dietary intake  (e.g., urinary sodium as a 
measure of dietary sodium intake, urinary potassium as a measure of fruit and 
vegetable intake);
o cardiorespiratory fitness, accelerometer measures, or pedometer measures for 
physical activity;
o body mass index or body weight for diet and physical activity;
o fasting and/or two-hour glucose or HbA1c for diet and physical activity
o plasma lipids or blood pressure for diet and physical activity.

Adherence to the behavioral recommendations, such as engaging in physical activity, 
following dietary recommendations, smoking cessation, and participating in stress 
reduction and health education programs, and improved quality of life, are of 
interest as indicators of success of the program(s) and acceptability.  In addition 
to specifying the primary outcome, applicants should propose and justify secondary 
outcome measures.  Although an extensive cost analysis is beyond the scope of this 
initiative, applicants must include a cost-effectiveness analysis.

7. Recruitment of Individuals and Communities. Applicants may propose to include one 
or more AI/AN communities to achieve the necessary sample size or otherwise enhance 
the scientific value of the study sample, within the strict budgetary constraints of 
this RFA.  Applicants should provide preliminary evidence of community support and 
of their ability to recruit participants in each community involved in the study, to 
implement measurement and intervention protocols in the target population, to 
provide appropriate  oversight, and to maintain high rates of follow-up throughout 
the intervention.   

Individuals recruited as part of a pre-existing study that is not an intervention 
study may be proposed for inclusion in the proposed study.  However, applicants must 
provide evidence that recruitment from an existing cohort will not unduly interfere 
with the goals of the existing study or that the cohort is no longer being studied.  
In addition, the application should include a justification for including such 
participants for the proposed protocol.  Applicants including participants from an 
extant study must submit, prior to the review, a letter from the principal 
investigator or steering committee of the parent study approving their 

8.  Quality Control and Data Management.  Applicants must describe their procedures 
for quality control of measurements and intervention delivery and provide 
preliminary evidence of their ability to achieve adequate quality control.  They 
must also describe their data management procedures. 

9.  Partnerships.  Tribes, communities, and organizations that do not have research 
experience are strongly encouraged to develop partnerships with research 
organizations.  Involvement of Native researchers and other appropriate 
professionals also is strongly encouraged.  Applicants are strongly encouraged to 
include a Native researcher as a co-investigator on this project in their 
application.  After the award, grantees may also submit an application for a 
minority supplement award for funding one or more AI/AN training positions; however, 
these awards are competitive and funding is not guaranteed. Guidelines for the 
minority supplement program can be found at:

10. Awareness of Strain on Existing Resources.  Investigators should be aware of the 
need to conduct this study without creating excessive strain on existing resources 
that are often functioning at, or above, capacity.  These existing resources include 
medical facilities, personnel, and equipment, as well as community infrastructure.  
Applicants should propose using facilities or systems for which they have tribal, 
community, or Indian Health Service approval, as appropriate, and provide written 
evidence thereof.

C. Dissemination Plan

A critical feature of this project is the development of interventions with the 
potential to be incorporated into the medical care systems, public-health system, 
and/or community structure of AI/AN communities, if the results demonstrate clinical 
effectiveness.  Intervention programs resulting in positive study outcomes may be 
disseminated to the communities in which the study was conducted, as well as other 
Native communities, at the completion of the research.  The application must include 
a dissemination plan that includes dissemination of study results as well as 
dissemination of intervention approaches and materials.  The dissemination plan 
should identify a target audience, describe methods to be used, and discuss how the 
intervention will be made translatable.  The dissemination plan should be updated at 
the end of the study when the results are known.  A budget not to exceed 5% of the 
total project budget may be proposed to implement the dissemination plan.  

D. Study Components

Grantee organizations will be tribes, communities, research organizations, or 
institutions that are actively involved in the recruitment, evaluation, and 
treatment of study participants.  Proposed studies may involve several tribes, 
communities, or sites.  Partnerships with tribes and/or communities are mandatory, 
if the tribe or community is not the grantee organization.

Each awardee will have primary responsibility for collecting, editing, storing, and 
analyzing their data.  Awardees should oversee implementation of their interventions 
and adherence to their protocols, and assure that appropriate quality control 
procedures are in place.  Each awardee will be responsible for training and 
certification of their personnel.

A Data and Safety Monitoring Board (DSMB) will be established to monitor data and 
oversee participant safety in each study supported by this initiative.  At the first 
meeting, the DSMB will review the awardee’s protocol.  Subsequently, the DSMB will 
monitor and review recruitment, adverse events, data quality, outcome data, and 
overall awardee performance.  It has the responsibility to review interim data and 
final data, and recommend whether the protocol should be modified, and whether the 
study should be continued or should be terminated early.  Thus, its ethical 
responsibilities to the participants, as well as to the integrity of the study, are 
of paramount importance to the NHLBI.  Members will be appointed by each awardee and 
approved by the NHLBI.  Members should not be from the awardee’s institution. The 
DSMB will report their recommendations to awardees, with a copy to the NHLBI.  The 
DSMB will meet at least twice annually, with at least one of the meetings being in 

Alternatively, the NHLBI may appoint a single DSMB for monitoring all of the funded 
projects.  This decision will be made after peer review.  In either event, 
applicants should not appoint DSMB members in advance of the peer review, or even 
inquire about the interest of possible DSMB members, because anyone so contacted 
would not be eligible to serve as a member of the peer reviewer committee that will 
evaluate the applications for scientific merit.  Awardees should budget for DSMB 
meetings, including travel, meeting rooms, and honoraria for DSMB members.
In addition to the semi-annual DSMB meetings, a meeting will be held in the 
Washington DC area with the NHLBI project office and the investigators from each 
site at least annually.  The investigators may form committees that would meet 
periodically by conference calls as needed.  Awardees should provide an estimate of 
the number of meetings and conference calls that may be needed and budget for them.

E. Time Line of the Project

The timeline for this initiative does not allow time for initial tribal and/or 
community protocol approval or approval of facilities after each study has begun.  
All such approvals must be submitted with the application.  IRB approvals must be 
submitted prior to the award.

The duration of the grants resulting from this RFA will be five years.  The time 
line after the awards are made is planned as follows, but may be modified as needed.  
Any modifications should be included in the grant application with justification.

In Year 01 the grantees will focus on: 1) conducting formative assessment measures 
through surveys, interviews, and focus groups to determine recruitment strategies 
and intervention methods to ensure community responsiveness to the study; 2) pilot 
testing screening and measurement procedures and data collection instruments;  3) 
training assessors and interventionists; and 4) submitting any protocol 
modifications for community and IRB approval.

In Year 02 the grantees will focus on: 1) recruiting and screening potential 
participants; 2) baseline measurements; 3) randomization of eligible participants; 
and 4) implementing the interventions.  

In Years 03 and 04 the grantees will continue the two-year interventions, and 
conduct followup assessment beginning in Year 04.  

In Year 05 the grantees will complete followup assessment during the first part of 
Year 05; during the second part of Year 05, grantees will conduct data analyses, and 
present and publish results from the study.  After approval by the NHLBI, 
dissemination plans will be implemented, which may be during a no-cost extension.


This RFA uses the cooperative agreement (U01) award mechanism. In the cooperative 
agreement mechanism, the Principal Investigator retains the primary responsibility 
and dominant role for planning, directing, and executing the proposed project, with 
NIH staff being substantially involved as a partner with the Principal Investigator, 
as described under the section "Cooperative Agreement Terms and Conditions of 
Award".   This RFA is a one-time solicitation.  Any future unsolicited, competing-
continuation applications based on this project will compete with all investigator-
initiated applications and will be reviewed according to the customary peer review 
procedures.  The anticipated award date is September 15, 2005.  Applications that 
are not funded in the competition described in this RFA may be resubmitted as NEW 
investigator-initiated applications using the standard receipt dates for NEW 
applications described in the instructions to the PHS 398 application.

This RFA uses just-in-time concepts. This program does not require cost sharing as 
defined in the current NIH Grants Policy Statement at 


The NHLBI intends to commit approximately $1.0 million in direct costs in Fiscal 
Year 2005 to fund four field Centers in response to this RFA.  Each applicant may 
request a project period of five years and a budget for direct costs of up to 
$250,000 for the first year, $425,000 for the second year, $450,000 for the third 
year, $475,000 for the fourth year, and $275,000 for the fifth year.  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 meritorious applications. A total of up to $7.5 million in 
direct costs is available over the five-year period for the project.  


You may submit (an) application(s) if your institution has any of the following 

o Sovereign tribal governments, AI/AN organizations sanctioned by tribes, 
agencies/programs that target or benefit AI/AN communities, and community groups
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, and 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Faith-based and community-based organizations 
o Foreign institutions are not eligible for receiving grants under this solicitation 
and domestic applications may not include international components. 


Any individual with the skills, knowledge, and resources necessary to carry out the 
proposed research is invited to work with his or her institution to develop an 
application for support.  Individuals from underrepresented racial and ethnic groups 
as well as individuals with disabilities are always encouraged to apply for NIH 

The Principal Investigator for each application is expected to possess certain 
essential qualifications: 1) strong scientific expertise in behavioral intervention 
studies, biobehavioral research, and/or biomedical research; 2) scientific 
leadership experience and a strong academic and scientific background, as 
exemplified by scientific publications and a record of peer-reviewed scientific 
support; 3) history of mutually beneficial and productive collaborations with the 
AI/AN communities participating in the proposed research and, if applicable, with 
the partners or subcontractors of the proposed study; 4) extensive supervisory 
experience; 5) knowledge of NIH grant and research policies, including those 
concerning human participants in research, human biological material, data 
management, and data privacy; and 6) knowledge of tribal/community processes for 
review and approval of research and research publications. 

This RFA may be of interest to researchers with expertise in the areas of behavioral 
sciences, prevention research, dietary and nutritional sciences, exercise science, 
minority health, epidemiology, biostatistics, and cardiology.  Experience with 
controlled community studies is desirable, but not required.  


Community Support Partnerships

Applications must include evidence of 1) strong scientific capabilities and 2) 
evidence of community involvement and support.  Applications that represent a 
partnership between a tribe or community and a research organization should include 
a resolution from the tribal or community government specifying that the community 
or tribe agrees to participate as a partner in the project and will strongly support 
the project for its entire duration.  Applications that include more than one tribe 
or community should include a resolution of support from each participating tribe 
and community.  If the application includes a consortium of tribes or communities, 
applicants must provide a resolution of support from each tribe or community of the 
consortium.  If the applicant is a tribally sanctioned non-profit tribal 
organization, specific tribal resolution(s) of support will not be required if the 
current tribal resolution(s) under which the organization operates encompasses 
activities proposed in the application.  A copy of the current operational 
resolution(s) should be submitted with the application.  Each AI/AN organization 
that participates in the project should also submit such a letter of support. 

Letters of support and/or resolutions should be placed in the grant application 
after the Literature Cited in section h. (Consortium/Contractual Arrangements) or 
section i. (Consultants), clearly labeled, and referenced in the body of the 
application, where the organizational structure is discussed. 

Tribal/community resolutions of support must explicitly stipulate that they agree to 
respond expeditiously to requests for approval of protocol modifications, approval 
of abstracts for presentations to scientific meetings, and approval of manuscripts 
submitted for publication in scientific journals.  The time required for approving 
each of these (protocol, abstracts, manuscripts): a) must be proposed and stated 
within the resolution of support, b) may differ for each of these activities; c) may 
be modified by study investigators only in consultation with the tribal/community 
leadership; and d) should identify an individual or entity within the tribe or 
community to whom a request for waiver of the time requirement can be directed if 
circumstances arise.  In the absence of a written waiver, study investigators may 
assume passive approval only after the established time interval has expired. 
Disapprovals must specify the reasons for disapproval explicitly, and describe the 
steps necessary for obtaining approval

Applications that represent a partnership between a tribe or community and a 
research organization should describe the scientific, logistic, and organizational 
responsibilities of each of the partners for each aspect of the proposed project.  
The application should also describe the history of the partners in collaborating on 
prior research projects, or other mutually beneficial activities, the mutual 
understanding and cooperation among the partners, and the relative contributions to 
the previous projects.

Applicants are strongly encouraged to provide work opportunities for AI/AN 
undergraduate, graduate, and postdoctoral students in behavioral and biomedical 

Applicants should obtain necessary clearance for their research protocols through 
all applicable Institutional Review Boards (IRBs), including their institutional 
IRB, the tribal or community IRB(s) if applicable, and the local and national Indian 
Health Service IRB if their research involves Indian Health Service facilities or 
personnel.  Applicants are requested to include in their clearance package 
descriptions of all intervention components for both the intensive intervention 
group(s) and the comparison group and descriptions of all measurements.  All 
required IRB approvals must be submitted to the NHLBI prior to the award of the 

Cooperative Agreement 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 the study, 
including any modification of study design, conduct of the study, quality control, 
data analysis and interpretation, preparation of publications, and collaboration 
with other investigators.

2.  An NHLBI Project Scientist will provide substantial assistance in the conduct of 
the awarded projects, and may serve as a member of subcommittees on the project.  
The NHLBI Project Scientist (and other NHLBI scientists as needed) may work with 
awardees on issues such as recruitment, intervention, follow-up, quality control, 
adherence to protocol, assessment of problems affecting the study, potential changes 
in the protocols, interim data and safety monitoring, final data analysis and 
interpretation, preparation of publications, and development of solutions to any 
major problems such as insufficient participant enrollment.   The final protocol and 
consent forms will be negotiated between the awardee and the NHLBI Project 
Scientist, and must be approved by the NHLBI based on recommendations from the DSMB.

3.  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 
Department of Health and Human Services (DHHS), Public Health Service (PHS), and NIH 
policies.  The NHLBI Project Scientist, on behalf of the NHLBI, will have the same 
access, privileges and responsibilities regarding the data as the other members of 
the project team.

4.  Support or other involvement of industry or any other third party in the study -
- e.g., participation by the third party; involvement of study resources or citing 
the name of the study or NHLBI support; or special access to study 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.

5.  Awardees are required to publish and to publicly release and disseminate 
results, data, and other products of the study.  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 
study Principal Investigators.  As part of the dissemination plan, at the end of the 
project, each awardee will provide a copy of the protocol and intervention materials 
to the NHLBI for use in dissemination. 

6.  The NHLBI reserves the right to terminate or curtail the studies (or an 
individual award) in the event of (a) substantial shortfall in participant 
recruitment, follow-up, data reporting, quality control, or other major breach of 
the protocol, (b) substantive changes in the agreed-upon protocol with which NHLBI 
cannot concur, (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.

7.  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 principal investigators of the awarded projects under this initiative or by 
the individual awardee in the event of an individual disagreement, a second member 
selected by the 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 DHHS regulation at 45 CFR part 16, or the rights of 
NHLBI under applicable statutes, regulations and terms of the award.

8.  These special terms of award are in addition to and not in lieu of otherwise 
applicable OMB administrative guidelines, DHHS Grant Administration Regulations at 
45 CFR part 74, and other DHHS, PHS, and NIH grant administration policy statements. 


We encourage inquiries concerning this RFA and welcome the opportunity to answer 
questions from potential applicants. Inquiries may fall into three areas: 
scientific/research, peer review, and financial or grants management issues:

o Direct inquiries regarding scientific/research issues to:

Jared B. Jobe, Ph.D.  
Division of Epidemiology and Clinical Applications 
National Heart, Lung, and Blood Institute 
6701 Rockledge Drive, Room 8120, MSC 7936 
Bethesda, MD 20892-7936 
Telephone: (301) 435-0407  
FAX: (301) 480-1773  

o Direct your questions about peer review issues to: 

Valerie L. Prenger, Ph.D. 
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7214, MSC 7924
Bethesda, MD  20892-7924
Zip code: Bethesda, MD 20817 (for express/courier service)
Telephone: (301) 435-0270
FAX: (301) 480-0730

o Direct your questions about financial or grants management matters to:
Ms. Tanya McCoy 
Grants Operations Branch
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7132, MSC 7926
Bethesda, MD  20892-7926
Telephone: (301) 435-0166
FAX:  (301) 480-3310


NHLBI plans to conduct several voluntary technical assistance and information 
sharing workshops about this RFA.  Two of these workshops will be conducted in 
conjunction with the Native American Research Centers for Health workshops; the 
first of these workshops has been tentatively scheduled for Albuquerque, New Mexico 
on April 21-22, 2004, and the second has been tentatively scheduled for May 17-18 in 
Portland, Oregon.   Another workshop has been tentatively scheduled in Scottsdale, 
Arizona in the afternoon of Tuesday May 11, 2004 in conjunction with the Indian 
Health Service Research Conference.   A presentation on the project will also be 
made at the National Council of Urban Indian Health Conference in Crystal City, 
Virginia on Monday May 3, 2004.  People planning to attend one of these workshops 
are asked to provide to the NHLBI the name of each person and of the organization 
each represents, no later than one week prior to these meetings to help insure that 
NHLBI brings enough copies of materials to the workshop.  Please provide the 
information to Jared B. Jobe at the email address listed under, “Where to Send 
Inquiries.”  Details about these workshops and information about the exact time and 
location of any additional workshop(s) can be obtained from Dr. Jobe.

Questions posed by applicants that are expected to have common interest will be 
posted, along with their answers on the same website as the minutes of the Working 
Group meetings:


Prospective applicants are asked to submit a letter of intent that includes the 
following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel
o Participating institutions
o 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 a subsequent application, the information that it contains allows 
NHLBI staff to estimate the potential review workload and plan the review.  The 
letter of intent is to be sent to Dr. Valerie L. Prenger at the address listed under 
“Where to Send Inquiries,” by the letter of intent receipt date.


Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001). Applications must have a Dun and Bradstreet 
(D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when 
applying for Federal grants or cooperative agreements. The DUNS number can be 
obtained by calling (866) 705-5711 or through the web site at The DUNS number should be entered on line 11 of 
the face page of the PHS 398 form. The PHS 398 document is available at in an interactive format.  
For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email:


See also the SPECIAL REQUIREMENTS for additional application instructions.

Checklist of what each application should include:

o a discussion of the cardiovascular health issues in the affected AI/AN populations 
and their prevalence.

Population, Recruitment, and Retention
o a description of the size and characteristics of the population to be recruited;  
o a description of participant eligibility criteria;
o the recruitment strategies to obtain and retain the required number of enrolled 
o evidence that the applicant can recruit and retain a sufficient number of eligible 
participants to complete the study;
o evidence of community involvement in the identification of the study population 
relevant to community needs.

Study Design and Intervention
o a description of the study design, including the unit of randomization 
(individual, family, school, or community);
o a proposal for behavioral interventions targeted to 1 or more behaviors or 
lifestyles for the Intensive Intervention Group(s) that affect CVD risk factors;
o a discussion of the theoretical background of the intervention(s);
o a description of any interventions planned for the comparison group, such as 
health education;
o a description of approaches to attain high levels of adherence to the 
o a description of how the intervention(s) are culturally appropriate and responsive 
to community issues or needs. 

o clear identification of the primary outcome and when it will be measured;
o a proposal for secondary and other outcome measures and when they will be 
o a description of approaches to maintain high rates of follow-up to measurement;
o evidence that the measures are culturally acceptable.

Quality Control Methods
o a description of initial and followup training for intervention and assessment 
o a description of methods for quality control for the adherence of staff to the 
o a discussion of possible problems and threats to internal and external validity 
and steps to be taken to minimize these potential problems;
o a discussion of other potential problem areas and possible solutions. 

o a description of power calculations and sample size needed to test specific 
hypotheses for experimental designs;
o a description of the statistical analysis plan; 
o a description of the expected magnitude of change in the targeted behaviors as a 
result of the intervention(s) and potential for impact on CVD risk and whether these 
differences are significant clinically or to public health;
o a discussion about how missing data will be handled;
o a description of the models for analyzing longitudinal data, if any;

o a description of the experience and expertise of study staff, including the 
principal investigator and co-investigators, and the experience and expertise of the 
research coordinator, recruitment coordinator, measurement staff, and 
interventionists, if they have been identified already;
o a description of the applicant’s experience and/or effectiveness in recruiting 
from and delivering interventions in AI/AN populations;
o a description of the organizational structure, delineating lines of authority and 
responsibility for addressing every aspect of a randomized controlled trial as 
o a succinct discussion of previous relevant investigational efforts; 
o a plan to hire community members when available for appropriate roles on the 
project (this requirement is described in more detail under BUDGET AND RELATED 
ISSUES below).

o  evidence of strong institutional support for the study, including adequate space 
in which to conduct intervention and assessment activities and office space for 
o evidence of adequate infrastructure for collecting, editing, storing, and 
analyzing their data. 

Partnerships and Approvals
o letters of resolution or participation from all tribal governments and community 
organizations participating in the study, as described under Community Support 
o description of the relationship between the partners and their roles and 
o a statement of willingness to collaborate with the NHLBI.

o a preliminary dissemination plan for the intervention, if found to be promising, 
including dissemination to NHLBI. 

o a detailed proposal for five budget periods of 12 months each and written 
justification (this requirement is described in more detail under BUDGET AND RELATED 
ISSUES below).

BUDGET AND RELATED ISSUES: Applications should contain five budget periods of 12 
months each.  Applicants should provide adequate written budget justification and 
include all applicable direct and F&A costs.  Applications must include estimates of 
staffing needs, including the principal investigator and other professional and 
support staff.  Applications must include estimates of travel costs for annual 
investigator meetings, and two annual  DSMB meetings (at least one must be in person 
in Bethesda, MD) to review the study progress, as detailed under the section on 
Special Requirements, along with statements indicating willingness to participate in 
these meetings.  Applications must include budget for staff to conduct data entry at 
their centers, for any equipment needed for data collection and intervention 
delivery, and for conference calls. 

Applications must include a plan to hire community members, when available, for 
appropriate roles on the project.  Each applicant is strongly encouraged, but not 
required, to include at least one AI/AN co-investigator on the study team, 
preferably a current or former community member or an enrolled tribal member.  Other 
appropriate roles for community members include, but are not limited to, research 
coordinators, recruiters, interventionists, assessors, and research assistants.  
Without regard to the number of AI/AN staff members and investigators hired by the 
study, additional scientist positions possibly can be added through the NIH Minority 
Supplement process (  

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) 
application form must be affixed to the bottom of the face page of the application.  
Type the RFA number on the label.  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 2 of 
the face page of the application form and the YES box must be marked. The RFA label 
is also available at:
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the 
application, including the Checklist, and three signed, photocopies, in one package 
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, as well as all 
five collated sets of Appendix material must be sent to Dr. Valerie Prenger at the 
address listed under, “Where to Send Inquiries.”  Applications must be received by 
the application receipt date listed in the heading of this RFA.  If an application 
is received after that date, it will be returned to the applicant without review.

APPLICATION PROCESSING: Applications must be received by the application receipt 
date listed in the heading of this RFA.  If an application is received after that 
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.  However, when a previously 
unfunded application, originally submitted as an investigator-initiated application, 
is to be submitted in response to an RFA, it is to be prepared as a NEW application.  
That is, the application for the RFA must not include an Introduction describing the 
changes and improvements made, and the text must not be marked to indicate the 
changes from the previous unfunded version of the application.  

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NHLBI.  Incomplete and/or nonresponsive applications will not 
be reviewed.  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 NHLBI in accordance with the review criteria stated below.  As part 
of the initial merit review, all applications will:

o Undergo a process in which only those applications deemed to have the highest 
scientific merit, generally the top half of the applications under review, will be 
discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the National Heart, Lung, and Blood Advisory 


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 evaluate the application in order to judge the 
likelihood that the proposed research will have a substantial impact on the pursuit 
of these goals. The scientific review group will address and consider each of the 
following criteria in assigning the application's overall score, weighting them as 
appropriate for each application. 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
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.

SIGNIFICANCE: Does this study address an important problem? If the aims of the 
application are achieved, could the project yield behavioral interventions that 
would impact cardiovascular mortality and morbidity in AI/AN? Is the underlying 
rationale for the study strong?

APPROACH:  Are the conceptual framework, design, methods, interventions, and 
analyses adequately developed, well-integrated, and appropriate to the aims of the 
project?  Are the informed consent procedures, randomization procedures, data 
collection, quality control, data management, and statistical analyses appropriate 
for the design and unit of randomization selected (individual, family, school, or 
community)?  Are the proposed outcome measure(s) objective measures of behaviors 
that the intervention targets? Does the applicant acknowledge potential problem 
areas and consider alternative tactics? 

POPULATION AND RECRUITMENT:  Is an adequate justification provided for the selection 
of the population to be studied?  What is the feasibility of the proposed project, 
as evaluated by plans to recruit communities and participants, plans delineating the 
feasibility and logistics of providing interventions to participants, and plans to 
assure community responsiveness and input?  Is the evidence sufficient to support 
community involvement or approval for participation of a parent study?

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?

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 other researchers (if any)?  Do the investigators have previous 
experience of prior effective partnerships with AI/AN communities? 

ENVIRONMENT: Does the scientific environment in which the work will be done 
contribute to the probability of success? Do the proposed studies take advantage of 
unique features of the scientific and cultural environment or employ useful 
collaborative arrangements? Is there evidence of institutional support? Have the 
investigators stated their willingness to collaborate with staff from the NHLBI?

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

o Protection of Human Subjects from Research Risk: The involvement of human subjects 
and protections from research risk relating to their participation in the proposed 
research will be assessed. (See criteria included in the section on Federal 
Citations, below).
o Inclusion of Women, Minorities, and Children in Research: The adequacy of plans to 
include subjects from both genders, all racial and ethnic groups (and subgroups), 
and children as appropriate for the scientific goals of the research.  Plans for the 
recruitment and retention of subjects will also be evaluated. (See Inclusion 
Criteria in the sections on Federal Citations, below).

o Research Sharing Data:

Applicants requesting more than $500,000 in direct costs in any year of the proposed 
research must include a data sharing plan in their application. The reasonableness 
of the data sharing plan or the rationale for not sharing research data will be 
assessed by the reviewers. However, reviewers will not factor the proposed data 
sharing plan into the determination of scientific merit or priority score.   
( and conflict of interest 
rules ( and data sharing 
policies of the NHLBI will be required 
(  Applicants who have any 
concerns about complying with the data sharing policies should briefly describe 
their concerns.  Some modifications may be negotiated in special circumstances, but 
NHLBI will retain final authority to decide what is acceptable.

o Dissemination Plans: The plans for the initial dissemination of successful 
intervention materials and interventions to AI/AN health care providers and 

o Budget:  The reasonableness of the proposed budget and the requested period of 
support in relation to the proposed research, as described under BUDGET AND RELATED 

Letter of Intent Receipt Date: September 22, 2004
Application Receipt Date: October 22, 2004
Peer Review Date: February-March 2005
Advisory Council Review: May 2005
Earliest Anticipated Start Date: September 2005


Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.


HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that applications 
and proposals involving human subjects must be evaluated with reference to the risks 
to the subjects, the adequacy of protection against these risks, the potential 
benefits of the research to the subjects and others, and the importance of the 
knowledge gained or to be gained. 

DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for all 
types of clinical trials, including physiologic, toxicity, and dose-finding studies 
(phase I); efficacy studies (phase II); efficacy, effectiveness and comparative 
trials (phase III).  The establishment of data and safety monitoring boards (DSMBs) 
is required for multi-site clinical trials involving interventions that entail 
potential risk to the participants.   (NIH Policy for Data and Safety Monitoring, 
NIH Guide for Grants and Contracts, June 12, 1998:  

SHARING RESEARCH DATA:  Investigators submitting an NIH application seeking $500,000 
or more in direct costs in any single year are expected to include a plan for data 
sharing or state why this is not possible.  Investigators should seek guidance 
from their institutions, on issues related to institutional policies, local IRB 
rules, as well as local, state and Federal laws and regulations, including the 
Privacy Rule. Reviewers will consider the data sharing plan but will not factor the 
plan into the determination of the scientific merit or the priority score.

requires education on the protection of human subject participants for all 
investigators submitting NIH proposals for research involving human subjects.  You 
will find this policy announcement in the NIH Guide for Grants and Contracts 
Announcement, dated June 5, 2000, at

Management and Budget (OMB) Circular A-110 has been revised to provide public access 
to research data through the Freedom of Information Act (FOIA) under some 
circumstances.  Data that are (1) first produced in a project that is supported in 
whole or in part with Federal funds and (2) cited publicly and officially by a 
Federal agency in support of an action that has the force and effect of law (i.e., a 
regulation) may be accessed through FOIA.  It is important for applicants to 
understand the basic scope of this amendment.  NIH has provided guidance at

Applicants may wish to place data collected under this RFA in a public archive, 
which can provide protections for the data and manage the distribution for an 
indefinite period of time.  If so, the application should include a description of 
the archiving plan in the study design and include information about this in the 
budget justification section of the application. In addition, applicants should 
think about how to structure informed consent statements and other human subjects 
procedures given the potential for wider use of data collected under this award.

Department of Health and Human Services (DHHS) issued final modification to the 
"Standards for Privacy of Individually Identifiable Health Information", the 
"Privacy Rule," on August 14, 2002.  The Privacy Rule is a federal regulation under 
the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs 
the protection of individually identifiable health information, and is administered 
and enforced by the DHHS Office for Civil Rights (OCR). 

Decisions about applicability and implementation of the Privacy Rule reside with the 
researcher and his/her institution. The OCR website ( 
provides information on the Privacy Rule, including a complete Regulation Text and a 
set of decision tools on "Am I a covered entity?"  Information on the impact of the 
HIPAA Privacy Rule on NIH processes involving the review, funding, and progress 
monitoring of grants, cooperative agreements, and research contracts can be found at

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals for NIH 
funding must be self-contained within specified page limitations. Unless otherwise 
specified in an NIH solicitation, Internet addresses (URLs) should not be used to 
provide information necessary to the review because reviewers are under no 
obligation to view the Internet sites.   Furthermore, we caution reviewers that 
their anonymity may be compromised when they directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving the 
health promotion and disease prevention objectives of "Healthy People 2010," a PHS-
led national activity for setting priority areas. This RFA is related to one or more 
of the priority areas. Potential applicants may obtain a copy of "Healthy People 
2010" at

AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal 
Domestic Assistance at and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health Systems 
Agency review.  Awards are made under the authorization of Sections 301 and 405 of 
the Public Health Service Act as amended (42 USC 241 and 284)(cite appropriate 
authorizations) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 
All awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants Policy 
Statement can be found at

The PHS strongly encourages all grant recipients to provide a smoke-free workplace 
and discourage the 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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Office of Extramural Research (OER) - Home Page Office of Extramural
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