UNDERSTANDING MECHANISMS OF HEALTH RISK BEHAVIOR CHANGE IN CHILDREN AND 
ADOLESCENTS

RELEASE DATE:  July 6, 2004

PA NUMBER: PA-04-121  

The R01 portion of this funding opportunity has been replaced by PA-07-148,
which now uses the electronic SF424 (R&R) application for February 5, 2007 
submission dates and beyond.

March 2, 2006 (NOT-OD-06-046) – Effective with the June 1, 2006 submission date, 
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using 
the electronic SF424 (R&R) application. This announcement will stay active for 
only the May 1, 2006 AIDS and AIDS-related application submission date for these 
mechanisms. The non-AIDS portion of this funding opportunity for these mechanisms 
expires on the date indicated below. Other mechanisms relating to this announcement 
will continue to be accepted using paper PHS 398 applications until the stated 
expiration date below, or transition to electronic application submission. 
Replacement R21 (PA-06-298) funding opportunity announcement
has been issued for the submission date of June 1, 2006 and submission dates 
for AIDS and non-AIDS applications thereafter.

EXPIRATION DATE for R21 Non-AIDS Applications: March 2, 2006
EXPIRATION DATE for R21 AIDS and AIDS-Related Applications: May 2, 2006 
Expiration Date for R01 Non-AIDS Applications: November 2, 2006 
Expiration Date for R01 AIDS and AIDS-Related Applications: January 3, 2007

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATIONS 
National Institutes of Health 
 (http://www.nih.gov)

COMPONENTS OF PARTICIPATING ORGANIZATION: 
National Institute of Child Health and Human Development (NICHD) 
 (http://www.nichd.nih.gov/)
National Cancer Institute (NCI)
 (http://www.nci.nih.gov/)
National Heart, Lung, and Blood Institute (NHLBI)
 (http://www.nhlbi.nih.gov)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
 (http://www.niaaa.nih.gov/)
National Institute on Drug Abuse (NIDA)
 (http://www.nida.nih.gov/)
National Institute of Nursing Research (NINR)
 (http://www.ninr.nih.gov) 
Office of Behavioral and Social Sciences Research (OBSSR)  
 (http://obssr.od.nih.gov/)
Office of Dietary Supplements (ODS)
 (http://dietary-supplements.info.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.865; 93.361; 93.399; 
93.837; 93.273; 93.279 

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this PA
o Research Objectives
o Mechanisms of Support
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS PA

The National Institute of Child Health and Human Development, the National 
Cancer Institute, the National Heart, Lung, and Blood Institute, the National 
Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug 
Abuse, the Office of Behavioral and Social Sciences Research, and the Office 
of Dietary Supplements invite research grant applications that will enhance 
our understanding of the factors and mechanisms that determine changes in 
health risk behaviors during childhood and adolescence. The concept of health 
risk behavior change is used in this program announcement to encompass the 
evolution of specific health impairing behaviors. Of particular interest are 
factors and processes that influence the initiation, continuation, and/or 
cessation of one or more of the following health risk behaviors:  (1) 
substance abuse, (2) inadequate exercise and poor dietary practices as they 
relate to being overweight or obese, and (3) intentional and unintentional 
injuries. The terms "health risk behaviors" and "risky behaviors" are used 
interchangeably in this PA.

The goal of this PA is to promote optimal physical and mental health in 
children and adolescents. This may be accomplished by research to enhance our 
understanding of the origin, evolution, and termination of health risk 
behaviors and, ultimately, by the development of effective prevention and 
intervention strategies designed to maintain healthy behaviors and prevent 
health risk behaviors. Interdisciplinary research is sought to explore the 
biological, genetic, physiological, psychological, and social/environmental 
factors and mechanisms that influence health risk behavior change in children 
and adolescents. A better understanding of theory-driven, causal pathways and 
recognition of mediators and moderators will aid in the identification of the 
etiology of health risk behaviors, precursors of health risk behaviors, and 
associated risk and resilience factors. The research findings will have the 
potential to inform the development of more comprehensive and effective 
prevention and intervention strategies in the fields of substance abuse, 
obesity, and injuries.

RESEARCH OBJECTIVES

Background

Many of the health risk behaviors of the 21st century result from voluntary 
behaviors such as unhealthy eating habits, the use of tobacco, alcohol or 
other drugs, and the failure to be physically active, maintain a healthy 
weight, or use safety equipment. Health risk behaviors, once considered the 
result of faulty decision-making, impulsive behavior, or characteristic of 
psychosocial development, are now recognized as dynamic conditions (some with 
genetic predispositions) evolving across the lifespan. Much research has been 
done to document various types of health risk behaviors, but little research 
has focused on understanding the mechanisms and contextual factors responsible 
for the process of behavior change. A biopsychosocial approach to the 
investigation of the mechanisms of health risk behavior change will explore 
the multiple spheres of influence provided by the individual, family, 
community, and society.

Childhood and adolescence are times of tremendous biological, cognitive, and 
psychosocial growth and development, taking children on a whirlwind trajectory 
from early childhood to young adulthood. Childhood and adolescence represent 
challenging targets for research aimed at understanding how health risk 
behaviors form; how they differ by individual, by ethnicity, and by gender; 
and the importance of genotype, phenotype, and the environment. Childhood 
offers a window of opportunity for the development of health promoting 
behaviors, but also represents a period of vulnerability for the formation of 
health risk behaviors. Further, transition points between childhood and 
adolescence are marked by widespread developmental changes in emotional, 
social, and cognitive development that may contribute to the development of 
health related behaviors in important ways. Health risk behaviors involve both 
genders and all socioeconomic, ethnic, and racial groups. 

Limited research exists on isolating process variables and causal pathways 
involved in the initiation, treatment, and cessation of health risk behaviors. 
The development of effective prevention and intervention strategies for health 
risk behaviors should include theory-driven models and hypotheses, and the 
identification and evaluation of mediators and moderators involved in the 
behavior change process.

The Healthy People 2010 objectives for the nation relate to improvements in 
the following leading health indicators:  physical inactivity, overweight and 
obesity, tobacco and other substance abuse, and injury and violence. The goal 
of Healthy People 2010, with its focus on prevention, is to achieve longer and 
healthier lives for individuals and the general population. Accomplishing this 
goal will be facilitated by the development of effective prevention programs 
based on an understanding of the motivations and determinants of health risk 
behaviors throughout childhood and adolescence. 

Overview of Current Research and Theory

Health risk behaviors such as tobacco, alcohol and other substance use, 
unhealthy dietary behaviors, and physical inactivity are evident in childhood 
and have far-reaching implications for individuals, families, and communities. 
Young people are trying illicit drugs at early ages, with almost one in three 
individuals having first experimented with alcohol (other than a few sips) 
before the age of 13 years. Alcohol consumption is a leading contributor to 
accidents, homicides, and suicides, the three leading causes of teen death. 
One in five youths has smoked a whole cigarette and one in ten youths has 
tried marijuana before turning 13 years of age. Cigarette smoking is the 
primary preventable cause of death in the United States. The majority of all 
American adult deaths results from cardiovascular disease and cancer, with 
many of the associated risk factors being initiated during adolescence. 
Substance abuse and the other health risk behaviors carry an enormous price 
tag in terms of the toll on life, quality of life, and economic costs. 

Health risk behaviors are monitored by surveys such as the Youth Risk Behavior 
Survey (YRBS), which in 2001 showed that 10.5 percent of high school students 
were overweight, 67.8 percent did not attend physical education class daily, 
28.5 percent had smoked cigarettes, and 78.6 percent had not eaten five 
servings of fruits and vegetables daily in the week preceding the survey. 
During the 30 days preceding the survey, 14.1 percent of high school students 
had rarely or never worn a seat belt, 30.7 percent had ridden with a driver 
who had been drinking alcohol, 13.3 percent of students nationwide had driven 
a car or other vehicle one or more times after drinking alcohol, 47.1 percent 
had drunk alcohol, 17.4 percent had carried a weapon, and 23.9 percent had 
used marijuana. In the 2002 “Monitoring the Future” Survey, 11.3 percent of 
12th graders were reported to have used illicit drugs other than marijuana in 
the month prior to the survey. 

The United States is facing an epidemic of childhood obesity, with poor 
dietary behaviors and high rates of physical inactivity contributing to this 
preventable health condition. In 1999 in the United States, 13 percent of 
children ages six to 11 years and 14 percent of adolescents ages 12 to 19 
years were overweight. The prevalence of overweight has nearly tripled for 
adolescents in the past two decades. And, though rising rates of overweight 
and obesity affect all racial, ethnic, socioeconomic, and education-level 
groups, they have disproportionately affected African Americans, Hispanics, 
and individuals from lower-income and lower-education brackets. 

One potential complication of obesity is type II diabetes mellitus, a 
condition also increasing by epidemic proportion. Other complications likely 
to follow the increase in obesity and type II diabetes include increases in 
cardiovascular disease, kidney failure, and blindness. Besides type II 
diabetes, overweight and obese children and adolescents are at risk of 
becoming overweight adults with problems of coronary artery disease, 
hypertension, stroke, respiratory problems, gallbladder disease, 
osteoarthritis, sleep apnea, and some forms of cancer. Obese individuals also 
face decreased productivity, social stigmatization, high health care costs, 
and premature death. Each year, 300,000 deaths in the U.S. are associated with 
obesity.

Physically inactive youth with low levels of cardiovascular fitness, high 
percentage of body fat, and large amounts of visceral adipose tissue have 
unfavorable cardiovascular risk profiles (e.g., low HDL, insulin resistance, 
and high triglycerides and LDL) which increase their risks of developing 
cardiovascular disease later in life. 

Although physical activity can help prevent excessive weight gain, more than a 
third of all middle and high school students do not get the recommended 30 
minutes of moderate physical activity on most days of the week. Regular 
exercise and participation in sports or physical education classes can have 
positive effects such as building and maintaining strong muscles and bones, 
controlling weight, and providing positive psychological benefits. Physical 
activity declines as children transition from childhood through adolescence. 
Children of lower socioeconomic status are less active than children of higher 
socioeconomic status and girls are less active than boys during adolescence. 

Unintentional injuries are the leading cause of death for individuals from age 
one to 24 years. Motor vehicle crashes, fires, and poisonings injure and kill 
thousands of children each year, despite the fact that a number of effective 
preventive strategies exist. Understanding factors that influence children's 
decisions to wear seat belts and bike helmets, and identifying motivational 
aids to enhance their compliance with safety devices, will inform prevention 
and intervention strategies and subsequently reduce unintentional injuries and 
deaths. 

For years, researchers have been intrigued by health risk behaviors and have 
expended extensive effort to observe, describe, predict, and prevent risky 
behaviors. Many health risk behaviors co-occur and co-vary in segments of the 
population, although the basis of the covariance is frequently unknown. 
Research is needed that moves beyond measuring variance in search of a 
comprehensive understanding of the processes and factors responsible for 
health risk behavior change. Numerous intervention and prevention programs 
have been implemented for substance abuse, physical inactivity, obesity, 
violence and injury prevention, yet the effectiveness in many cases has been 
limited and the results have been short term. It is apparent that providing 
factual information concerning the dangers and negative consequences 
associated with health risk behaviors is not sufficient to deter all 
individuals from participating in high risk health behaviors. Understanding 
why some individuals are risk takers, the timing of their health risk 
behaviors, and the factors that influence their decisions and actions are all 
important in advancing the field of child and adolescent health risk behavior. 

Although a number of theories have been developed to explain adult behavior 
change, few have considered the multiple systems of influence and the 
complexity of their combined effects on behavior change in children and 
adolescents. Theoretical models relevant to health and risk behavior include 
the following:  self-regulation theory (Kanfer, 1970), health belief model 
(Rosenstock, 1974), theory of reasoned action (Fishbein and Ajzen, 1975), 
subjective culture and interpersonal relations theory (Triandis, 1977), 
protection motivation theory (Maddux and Rogers, 1983), theory of planned 
behavior (Ajzen, 1985), self-determination theory (Deci & Ryan, 1985), 
transtheoretical model of behavior change (Prochaska, DiClemente, and 
Norcross, 1992), social cognitive theory (Bandura, 1994), and the ecological 
models (Sallis and Owen, 1999; Marshall and Biddle, 2001).

Behavioral change theorists have identified a number of factors believed to 
play important roles including attitudes, intentions, skills, emotions, self-
standards, self-efficacy, social norms, intrinsic and extrinsic motivation, 
and environment. Neuroscientists are discovering more about the complex 
changes in neurobehavioral systems with underpinnings that control behavior 
and emotion. This Program Announcement welcomes the behavioral, biobehavioral, 
and neuroscience communities to engage in the search for causal pathways to 
health risk behaviors. 

Research Scope

The health risk behaviors of interest to this PA include:  (1) substance 
abuse, (2) physical inactivity and poor dietary practices, and (3) intentional 
and unintentional injury. These topics were selected because each represents a 
significant risk to the health and well being of youth, with subsequent social 
and health implications during adulthood. These important health risk 
behaviors are amenable to short-term change in some cases and, at times, to 
long-term change. Additionally, these health risk behaviors have a high co-
occurrence in individuals; it is important to understand factors that 
contribute to the development of each risky behavior independently, as well as 
the possible synergistic, additive, or dynamic interaction of these risk 
behaviors. 

Studies of interest may be observational, epidemiological, interventional, 
secondary data analyses (i.e., analysis of existing data), and cost/benefit 
analyses. A multidisciplinary approach is encouraged and research findings 
from fields such as developmental pediatrics, psychology, behavioral science, 
neuroscience, neuropsychology, business, education, public policy, and others 
will be considered.

Health risk behaviors are influenced by a multitude of genetic, social, 
environmental, psychological, and physiological factors. Intrinsic factors 
such as genetic makeup, temperament, and memory of prior experiences combine 
with social and environmental factors to influence the physical, emotional, 
and intellectual development of an individual. Applicants are encouraged to 
expand upon current theories of behavior change and to consider techniques, 
strategies, and other models such as intrinsic and extrinsic motivation, 
motivational interviewing, feedback interventions, contingency management, 
social marketing, innovation diffusion, behavioral extinction, behavioral 
momentum/choice theory, contingency management techniques, behavioral 
economics, models of decision-making, and goal-directed behaviors. Numerous 
skills are involved in behavior change and should be considered for 
applications responding to this PA. These skills include self-monitoring 
(self-awareness), goal setting (realistic and specific), cognitive 
restructuring, stress management, mental imagery, relapse prevention skills, 
time management, conflict resolution, assertiveness skills, decision making 
skills, and substituting healthy behaviors for unhealthy behaviors. 
Identifying skills absent or ineffective in health risk behaviors and also 
those that are linked to healthy behaviors will be helpful.

Both internal and external (contextual) factors contribute to an individual's 
propensity to engage in or refrain from health risk behaviors. What these 
factors are, how they interact, for whom, and when in the developmental 
trajectory, are all questions of importance in understanding health risk 
behaviors and behavior change. 

Examples of research questions designed to fill gaps in our understanding of 
mechanisms and factors responsible for substance abuse, physical inactivity 
and poor dietary practices, and intentional and unintentional injuries 
include, but are not limited to, the following: 

(1) Biological Influences on Substance Abuse, Physical Inactivity and Poor 
Dietary Practices, and Injuries

o What are the basic biological factors and processes involved in the 
evolution of health risk behaviors? 

o What determines for whom and when in the developmental trajectory risk 
behaviors occur? 

o What neurochemical factors/processes and neuroanatomical circuits are 
involved in health risk behavior change and how do these systems evolve over 
time?

o What can newer imaging techniques contribution to our understanding of the 
links between neuroscience (developing brain) and behavioral science (health 
risk behavior)? 

o What are the bi-directional influences of physiological contributions, 
(neurobiological, endocrine, and immune) to risk behaviors, and how do changes 
to the neural, endocrine, and immune systems over the developmental trajectory 
influence health-risk behaviors? 

o What explains the differences and similarities in risk taking behavior by 
age and gender? 

o What are the genetic predispositions to health risk behavior and how do 
resilience factors (such as parental attachment and school connectedness) 
attenuate genetic influences?

o Does prenatal exposure to stress and/or teratogens (alcohol, tobacco, drugs 
of abuse) contribute to the offsprings' propensity to participate in health 
risk behaviors and, if so, how? 

o How do individuals identify, evaluate, differentiate, perceive, and 
internalize the inherent danger of health risk behaviors? 

o How do biological and experiential influences interact in the process of 
health risk behavior? How do these interactions change across childhood and by 
gender?

o How does communication (parent/child or peer/peer) influence health risk 
behaviors? 

o What interactions occur between sensation, perception of risk, emotion, 
learning, and memory and how do these interactions influence risk behavior?

o What roles do physiologic states and changes induced by pain, sleep 
deprivation, level of arousal, and exposure to drugs or hormones play in 
health risk behaviors?

o What effect does stress have on health risk behavior? 

(2) Psychological Influences on Substance Abuse, Physical Inactivity and Poor 
Dietary Practices, and Injuries

o What roles do metacognitive insight, risk perception, attention, beliefs, 
cognition, decision making, judgment, memory, self-regulation, sensation 
seeking, prosocial activity, goal setting, spirituality, and moral values play 
in risky behavior? 

o What is the role of prior experiences in current and future health risk 
behavior?

o What are the roles of aggression, impulsivity, and antisocial behavior in 
risk behavior?

o Can the developmental timeline for risk factors be shortened?

o What is the role of emotion (including reactivity and regulation) and how 
does the goal to elicit positive emotions or to avoid negative emotions affect 
an individual's current state of mind and willingness to participate in risk 
behavior?

o What is the role of orientation to present versus future in risk behavior?

o How can researchers study risk behavior under real world social and 
emotional conditions?

(3) Contextual Influences on Substance Abuse, Physical Inactivity and Poor 
Dietary Practices, and Injuries

o What roles do contextual factors play in health risk behaviors?

o How do parenting styles and behaviors, culture, and the socialization 
process influence children's health risk behavior? 

o What bi-directional effects on risky behavior occur as a result of the clash 
between parenting style and child's temperament? How are these conflicts 
between parenting style and child's temperament tempered by time and 
experience?

o What impact do social and contextual factors have on biological factors that 
influence health risk behavior?

o Which environmental groups (peer, family, and other social groups) influence 
health risk behavior and how? 

o How and why do resilience factors develop and can they be promoted at 
earlier ages?

o What is the role of environmental feedback in risk behavior? 

o How do environmental opportunities (gangs, cliques, money, social capital) 
promote or prevent risk behaviors? How critical is timing and type of 
opportunity?

o What is the role of the media in promoting health risk behavior and how can 
this be counteracted during childhood and adolescence?

o What are the essential elements (content, delivery, deliverer, timing) in 
effective health promotion messages and programs?

o How can health promotion messages be tailored effectively for younger 
children? What are the roles of reinforcement (booster) messages to prevent 
future risk behavior? 

(4) Co-occurring Health Behaviors

o Which health risk behaviors co-occur and co-vary in youth and why? 

o What linkages exist between healthy and unhealthy behaviors during childhood 
and adolescence?

o What are the connections between multiple unhealthy behaviors?

o Which co-occurring mental health conditions are associated with health risk 
behaviors in youth and what is the relationship?

o Are health risk behaviors more common in children with disorders of 
attention, emotion regulation, or learning and, if so, why?

MECHANISM OF SUPPORT

This PA will use the NIH Research Project Grant (R01) and 
Exploratory/Developmental Grant (R21) award mechanisms. As an applicant, you 
will be solely responsible for planning, directing, and executing the proposed 
project. 

The R01 should be used for full-scale research projects. 

The Exploratory/Developmental Grant (R21) is intended to encourage new 
exploratory and developmental research projects, including high risk research 
that may lead to a breakthrough in a particular area, or to the development of 
novel techniques, agents, methodologies, models or applications that could 
have major impact on biomedical, behavioral, or clinical research. Examples 
include feasibility testing for a novel area of investigation or a new 
experimental system with potential to enhance health-related research, and the 
unique and innovative use of an existing methodology to explore a new 
scientific area. For the R21 award, the applicant may request a project period 
of up to two years with a combined budget for direct costs of up $275,000 for 
the two-year period. For example, the applicant may request $100,000 in the 
first year and $175,000 in the second year. The request should be tailored to 
the needs of the project. Normally, no more than $200,000 may be requested in 
any single year. The NIH Exploratory/Developmental Award is explained in 
detail at http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html. 

This PA uses just-in-time concepts.  It also uses the modular as well as the 
non-modular budgeting formats (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).  Specifically, if 
you are submitting an application with direct costs in each year of $250,000 
or less, use the modular format.  Otherwise follow the instructions for non-
modular research grant applications.  This program does not require cost 
sharing as defined in the current NIH Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2001/part_I_1.htm.

ELIGIBLE INSTITUTIONS

You may submit an application if your institution has any of the following 
characteristics: 

o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments 
o Eligible agencies of the Federal government  
o Domestic or foreign institutions/organizations 
o Faith-based or community-based organizations 

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with his/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 programs.   

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA and welcome the opportunity 
answer questions from potential applicants.  Inquiries may fall into two 
areas:  scientific/research and financial or grants management issues:

o Direct your questions about scientific/research issues to:  

Lynne Haverkos, M.D., M.P.H.
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
6100 Executive Boulevard, 4B05, MSC 7510
Bethesda, MD  20892-7510
Telephone: (301) 435-6881
FAX: (301) 480-0230
Email:  haverkol@mail.nih.gov 

Louise C. Mâsse, Ph.D. 
Division of Cancer Control and Population Sciences
National Cancer Institute
6130 Executive Boulevard, Room 4076, MSC 7335
Bethesda, MD 20892-7335
Telephone: (301) 435-3961
FAX: (301) 480-2087
Email:  massel@mail.nih.gov 

Charlotte Pratt, Ph.D., R.D.
Division of Epidemiology and Clinical Applications
National Heart, Lung and Blood Institute
6701 Rockledge Drive, Room 8134, MSC 7936
Bethesda, MD 20892-7936 
Telephone: (301) 435-0382
FAX: (301) 480-1669
Email:  prattc@nhlbi.nih.gov 

Cherry Lowman, Ph.D.
Division of Treatment and Recovery Research
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 2051, MSC 9304
Bethesda, MD 20892-9304
Telephone: (301) 443-0637
FAX: (301) 443-8774
Email:  clowman@niaaa.nih.gov 

Kathleen Etz, Ph.D.
Division of Epidemiology, Services, and Prevention Research
National Institute on Drug Abuse
6001 Executive Boulevard, Room 5163, MSC 9589
Rockville, MD 20892-9589
Telephone: (301) 443-1514
FAX: (301) 443-2636
Email:  etzk@mail.nih.gov 

Yvonne Bryan, Ph.D., R.N.
Office of Extramural Programs
National Institute of Nursing Research
6701 Democracy Boulevard, Room 710, MSC 4870
Bethesda, MD 20892-4870
Telephone: (301) 594-6908    
FAX: (301) 480-8260
Email:  bryany@mail.nih.gov 

o Direct your questions about financial or grants management matters to:  

Lisa Moeller
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, 8A17, MSC 7510
Bethesda, MD  20892-7510
Telephone: (301) 496-5482
FAX: (301) 402-0915
Email: moellerl2@mail.nih.gov

Aida Vasquez
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243, MSC 7150
Bethesda, MD 20892-7150
Telephone: (301) 496-2736
FAX: (301) 496-8601
Email:  vasquez@mail.nih.gov  

Kieran Kelley
Senior Grants Management Specialist
National Heart, Lung and Blood Institute
6701 Rockledge Drive, Room 7170, MSC 7926
Bethesda, MD 20892-7926
Telephone: (301) 435-0154 
FAX: (301) 480-3310 
Email:  kelleyk@nhlbi.nih.gov 

William Caputo
Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3027, MSC 9304
Bethesda, MD 20892-9304
Telephone: (301) 443-2434
FAX: (301) 443-3891
Email:  bcaputo@mail.nih.gov 

Gary Fleming
Grants Management Branch
National Institute on Drug Abuse
6101 Executive Boulevard, Suite 242, MSC 8403
Bethesda, MD 20892-8403
Telephone: (301) 443-6710
FAX: (301) 594-6849
Email:  gf6s@nih.gov 

Lawrence Haller
Office of Grants/Contract Management
National Institute of Nursing Research 
6701 Democracy Boulevard, Room 710, MSC 4870
Bethesda, MD  20892-4870
Telephone: (301) 402-1878
FAX:  (301) 451-5652
Email:  hallerl@mail.nih.gov 
 
SUBMITTING AN APPLICATION

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 http://www.dunandbradstreet.com/. The DUNS number 
should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 
is available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an 
interactive format.  For further assistance contact GrantsInfo, Telephone 
(301) 435-0714, Email: GrantsInfo@nih.gov.

The title and number of this program announcement must be typed on line 2 of 
the face page of the application form and the YES box must be checked.

SUPPLEMENTARY INSTRUCTIONS:  Instructions contained in the NIH 
Exploratory/Developmental Grant Program Announcement 
(http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html) should be 
followed when submitting an R21 application.

APPLICATION RECEIPT DATES:  Applications submitted in response to this program 
announcement will be accepted at the standard application deadlines, which are 
available at http://grants.nih.gov/grants/dates.htm.  Application deadlines 
are also indicated in the PHS 398 application kit.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS:  Applications requesting 
up to $250,000 per year in direct costs must be submitted in a modular grant 
format.  The modular grant format simplifies the preparation of the budget in 
these applications by limiting the level of budgetary detail.  Applicants 
request direct costs in $25,000 modules.  Section C of the research grant 
application instructions for the PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step 
guidance for preparing modular grants.  Additional information on modular 
grants is available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR:  
Applications requesting $500,000 or more in direct costs for any year must 
include a cover letter identifying the NIH staff member within one of NIH 
institutes or centers who has agreed to accept assignment of the application.   

Applicants requesting more than $500,000 must carry out the following steps:
   
1) Contact the IC program staff at least six weeks before submitting the     
application, i.e., as you are developing plans for the study; 

2) Obtain agreement from the IC staff that the IC will accept your         
application for consideration for award; and,
  
3) Identify, in a cover letter sent with the application, the staff member       
and IC who agreed to accept assignment of the application.  

This policy applies to all investigator-initiated new (type 1), competing 
continuation (type 2), competing supplement, or any amended or revised version 
of these grant application types. Additional information on this policy is 
available in the NIH Guide for Grants and Contracts, October 19, 2001 at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html. 

SENDING AN APPLICATION TO THE NIH:  Submit a signed, typewritten original of 
the application, including the checklist, and five signed photocopies in one 
package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

APPLICATION PROCESSING:  Applications must be mailed on or before the receipt 
dates described at 
http://grants.nih.gov/grants/funding/submissionschedule.htm. 

The CSR will not accept any application in response to this PA that is 
essentially the same as one currently pending initial review unless the 
applicant withdraws the pending application.  The CSR will not accept any 
application that is essentially the same as one already reviewed.  This does 
not preclude the submission of a substantial revision of an application 
already reviewed, but such application must include an Introduction addressing 
the previous critique.

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within eight weeks.

PEER REVIEW PROCESS

Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review group 
convened in accordance with the standard NIH peer review procedures 
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific 
and technical merit.  

As part of the initial merit review, all applications will:

o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the appropriate national advisory council 
or board.

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to evaluate 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, how will scientific knowledge be advanced?  What 
will be the effect of these studies on the concepts or methods that drive this 
field?

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

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)?

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

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following 
items will be considered in the determination of scientific merit and the 
priority score:

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 
(http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm). (See 
criteria included in the section on Federal Citations, below.)

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 will be assessed.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the sections on 
Federal Citations, below.)

ADDITIONAL REVIEW CONSIDERATIONS 

SHARING RESEARCH DATA:  Applicants requesting $500,000 or more in direct costs 
in any year of the proposed research are expected to 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. 

BUDGET:  The reasonableness of the proposed budget and the requested period of 
support in relation to the proposed research.

AWARD CRITERIA

Applications submitted in response to a PA will compete for available funds 
with all other recommended applications.  The following will be considered in 
making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds
o Relevance to program priorities

REQUIRED FEDERAL CITATIONS

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  
(http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

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: http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

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  
(http://grants.nih.gov/grants/policy/data_sharing).  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.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH:  It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of the 
research.  This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts 
on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.  
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that:  a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; and 
b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:  
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported by 
the NIH, unless there are scientific and ethical reasons not to include them.  

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:  NIH 
policy 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 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT:  The 
Office of 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 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA 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.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  The 
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 
(http://www.hhs.gov/ocr/) 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 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

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 PA 
is related to one or more of the priority areas.  Potential applicants may 
obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS:  This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ 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) 
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 
http://grants.nih.gov/grants/policy/policy.htm.  

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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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