HIV/AIDS, DRUG USE, AND HIGHLY VULNERABLE YOUTH: TARGETING RESEARCH GAPS 

RELEASE DATE:  January 15, 2004

RFA NUMBER:  RFA-DA-04-012  

Department of Health and Human Services (DHHS)

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

COMPONENTS OF PARTICIPATING ORGANIZATION:
National Institute on Drug Abuse (NIDA) 
 (http://www.nida.nih.gov)
National Institute of Mental Health (NIMH) 
 (http://www.nimh.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER:  93.279 (NIDA), 93.242 (NIMH)

LETTER OF INTENT RECEIPT DATE:   February 17, 2004
APPLICATION RECEIPT DATE:        March 17, 2004 

THIS REQUEST FOR APPLICATIONS (RFA) CONTAINS THE FOLLOWING INFORMATION:

o Purpose of this RFA
o Research Objectives
o Mechanisms of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA 

The National Institute on Drug Abuse (NIDA) and the National Institute of 
Mental Health (NIMH) invite innovative applications to address critical gaps in 
research on HIV/AIDS prevention, treatment, and related health issues among 
highly vulnerable youth.  For the purpose of this RFA, highly vulnerable youth 
are those children, adolescents, and young adults aged 10-24 years who are 
using or are at high-risk for using drugs (both injection and non-injection 
drug use) and who are (a) at high risk for HIV and other infectious diseases 
(e.g., hepatitis B virus (HBV), hepatitis C virus (HCV), (b) living with 
HIV/AIDS, and/or (c) affected by HIV/AIDS (e.g., youth with family living with 
HIV, especially youth from drug-using households; youth bereaved by HIV, 
including youth orphaned by HIV/AIDS).    

This initiative is focused on highly vulnerable youth in the United States who 
are particularly vulnerable to HIV/AIDS and its medical and psychosocial 
consequences: (a) youth in risky social environments who are exposed to 
multiple factors associated with drug abuse and HIV, but who have limited 
exposure to factors that are protective, (b) youth who live outside of the 
protective influences of traditional family, school, or work venues (e.g., on 
the street, homeless and runaway youth, youth in foster care, incarcerated 
youth, youth in gangs, migrant youth), (c) youth who represent the current or 
emerging face of the HIV epidemic in the U.S. (e.g., young minority females, 
young men who have sex with men, youth from rural or suburban areas), and (d) 
youth in families and/or communities already vulnerable as a result of poverty, 
HIV/AIDS, drug abuse, mental illness, stigma, discrimination, and violence.

The overall objective of this RFA is to facilitate the development and 
implementation of interventions that reduce HIV infections and mitigate the 
medical and psychosocial consequences of the virus in order to improve the 
health and quality of life of youth at risk for, living with, or affected by 
HIV/AIDS.  This RFA encourages innovative, culturally relevant, and gender 
sensitive research in the following areas: (a) epidemiology of current and 
emerging trends related to HIV/AIDS and drug use patterns, physical and mental 
health comorbidities, and social environments among highly vulnerable youth; 
(b) development, implementation, evaluation, and dissemination of innovative 
approaches to prevent the transmission of HIV infection; (c) access to, receipt 
of, and adherence to health and drug abuse treatment services, including 
research on barriers to treatment such as stigma, and on optimizing HIV/AIDS 
risk reduction through drug abuse treatment; (d) integration of services (e.g., 
HIV/AIDS prevention and treatment services, HIV/AIDS medical services with drug 
abuse prevention and/or treatment, HIV/AIDS and HBV/HCV prevention).   

RESEARCH OBJECTIVES

Background

In the third decade of the pandemic, HIV/AIDS continues to impact global 
health.  An estimated 40 million people were living with HIV/AIDS in 2002 with 
5 million new infections that year.  In many areas of the world, including 
communities in the U.S., youth (those under 25 years) represent the component 
of the population at greatest risk for HIV infection, with young females often 
at highest risk.  More than a third of people living with HIV globally and over 
half of persons newly infected in 2002 were under age 25.  In the U.S., an 
estimated 900,000 people are living with HIV/AIDS, with 40,000 new HIV 
infections estimated each year, almost a quarter of these are among youth.  
While new infection rates in the U.S. are low in comparison with countries that 
have been devastated by the epidemic, the impact of the virus on individuals, 
families, and communities remains high.  In the U.S., HIV disproportionately 
affects minority communities, and those infected are increasingly young, 
female, and minority.  Among adolescents, young African American women and 
young men who have sex with men, particularly young men of color, are at high 
risk, as are young injection drug users (IDUs).  

Despite the existence of a highly effective vaccine, HBV continues to be highly 
prevalent in the U.S., with approximately 1.25 million chronic infections. An 
estimated 78,000 new infections, and 22,000 acute clinical cases occurred in 
the U.S. in 2001.  The highest rates of acute disease are among 20-49 year 
olds; 20 percent of acute cases reported to the CDC from 1980-1990 occurred 
before age 21. Acute HBV is disproportionately reported by communities of color 
and by men.  As with HIV, HBV is transmitted through unprotected sex and IDU.  
However, HBV is estimated to be about 100 times more infectious than HIV, with 
more rapid acquisition of HBV after initiating IDU.  Reaching adolescents with 
HBV vaccination before initiating high-risk practices is crucial.  
An estimated 3.9 million persons in the civilian non-institutionalized U.S. 
population have been infected with HCV, of whom approximately 2.7 million are 
chronically infected.  The highest incidence of acute HCV is found among 
persons aged 20-39 years.  The incidence of HCV is higher for males than 
females and the prevalence higher for African Americans than whites.  IDU is 
the major risk factor for HCV infection, accounting for 60 percent of newly 
reported cases.  HCV infection is acquired more rapidly after the initiation of 
IDU than either HBV or HIV infection; about one-third of IDUs are infected 
within two years of initiation, down from a high of 80 percent reported in the 
1980s.  Although the number of cases of acute HCV among IDUs has declined since 
1989, both the incidence and prevalence of HCV infection remain high.  Youth-
focused research on HCV prevention, treatment, and care is lacking. 
Highly Vulnerable Youth

Many youth in the U.S. are at high risk for infection with HIV/AIDS, HBV, HCV, 
and other infectious diseases as a result of engagement in high risk sexual 
and/or drug use behaviors (e.g., unprotected sexual intercourse, injection drug 
use, exchanging sex for drugs or goods).  Youth who live in social environments 
with high exposure to risk factors and limited exposure to protective factors 
as well as youth outside of the protective influences of traditional family, 
school, or work venues are at particular risk.  High rates of HIV-risk 
behaviors are reported for incarcerated youth, youth in foster care, youth 
receiving psychiatric care, youth involved with gangs, and homeless, on the 
street, and runaway youth.  For example, high rates of HIV, HBV, HCV, and STIs 
are reported among the estimated 500,000 to two million homeless youth in the 
U.S.  HIV-risk behaviors including substance abuse, lifetime IDU, needle 
sharing, and participation in survival sex (i.e., exchanging sex for food, 
shelter, drugs, or money) are also high. Despite their risky behavioral 
practices, these youth report an interest in learning and engaging in methods 
to protect their health.   

Over 30,000 young people have been reported with AIDS with estimates of over 
100,000 youth living with HIV/AIDS.  Research with youth infected through 
horizontal transmission indicates engagement in HIV-risk behaviors, including 
unprotected sexual intercourse and substance abuse.  Less is known about the 
risk behaviors of youth infected through vertical transmission who are aging 
into adolescence.  In addition to the common challenges associated with 
pubertal development, youth living with HIV face the additional challenges 
associated with living with a chronic illness including complex therapeutic 
drug regimens and decisions regarding disclosure of their conditions to peers.  
In addition, youth vulnerable to the consequences of HIV infection often live 
in communities with high exposure to risk and limited access to services.  
Prevention interventions that address drug-related risk behavior are needed for 
youth living with HIV to reduce the possibility of reinfection and additional 
HIV transmissions and maintain health status.  In addition, given the CDC 
estimates that one third of infected individuals are unaware of their HIV 
status, innovative research is needed on interventions that link infected youth 
to care.  

With over 900,000 persons in the U.S. estimated living with HIV, there are 
millions of youth affected by the virus and its medical and psychosocial 
consequences vis-à-vis parents, caregivers, siblings, partners, friends, and 
neighbors.  It is estimated that over 100,000 children have been orphaned by 
HIV/AIDS in the U.S; worldwide the estimate is a staggering 14 million 
children.  Affected youth may experience psychosocial and economic stresses 
associated with caring for a person with a chronic illness, or with grieving a 
parent or loved one who is dying or deceased.  Children of women infected 
through drug use risk behaviors, especially IDUs and their sexual partners, 
experience multiple challenges related to parental illness and to drug abuse, 
situations associated with risk for substance abuse, mental health, and 
behavioral problems.  Furthermore, many affected youth live in communities 
already vulnerable as a result of poverty, HIV/AIDS and other infectious 
diseases, drug abuse, violence, discrimination, and stigma.  While research 
indicates that interventions can reduce risk behaviors of HIV affected youth, 
many communities are unable to benefit from these or other health interventions 
due to limited access to prevention, treatment, and other health services. 
 
Social/contextual, developmental, and gender-related factors can influence HIV risk 
behavior and should be taken into consideration when designing prevention, 
treatment, and care interventions.  Factors such as gender norms, stigma, 
discrimination, homelessness, poverty, unemployment, and neighborhood 
characteristics can impact individuals’ HIV risk behaviors and the effectiveness and 
access to interventions to reduce HIV and related consequences.  For example, 
economic inequalities associated with youth status or poverty can result in 
increased exposure to risk factors as well as limited access to protective factors 
such as access to HIV/STD prevention and treatment services.  Risk and protective 
factors and corresponding avenues of intervention can vary across developmental 
period.  For example, adolescent females are more vulnerable to HIV/AIDS than adult 
women due to their immature reproductive organs.  High rates of STDs among 
adolescents also increase vulnerability to HIV/AIDS; approximately one-quarter of 
the 15 million incident cases of STDs reported in the U.S. each year are among 
teenagers.  In terms of cognitive and emotional development, adolescence is 
associated with perceptions of invulnerability and increased risk-taking and 
experimentation that occur in a context of developing biological, cognitive, 
emotional, and social capacities.  Relatedly, substance use and abuse increases 
across adolescence.  As youth develop, susceptibility or protection conferred vis-à-
vis particular risk mechanisms can also change (e.g., the changing role of family 
and peer influence across adolescence).  

Research on gender and HIV/AIDS has demonstrated gender differences across many 
areas of HIV research including but not limited to biological susceptibility, viral 
load, HIV related risk behaviors and their mediators, effectiveness of prevention 
interventions, access to prevention and care, and engagement in research studies.  
In addition to biological differences, a variety of social contextual factors 
including gender roles, gender norms, inequalities, substance abuse histories, 
experiences of sexual and physical abuse, and access to resources may be impacting 
outcomes.  Gender specific interventions may be required for some sub-populations of 
highly vulnerable youth; at minimal, gender analysis of risk factors and 
intervention effects are necessary. 

It is important to note that youth at highest risk experience multiple areas of 
vulnerability.  Thus, the need for multifaceted and multilevel interventions is 
greatest where there is greatest risk.  For example, many street youth are 
exposed to multiple risk factors: incarceration, foster care, living with HIV, 
HBV or HCV, substance abuse, psychiatric illness, physical and/or sexual abuse, 
economic inequalities, stigma, discrimination, and violence.  Furthermore, the 
problems that these youth face are compounded by poor access to health care. 
Interventions are needed to address the multiple levels and types of risk and 
protection factors that influence highly vulnerable youth including peer, 
family, partner, community and structural levels as well as individual level 
biological, cognitive, emotional, and social factors. 

This RFA is designed to address critical gaps in research on HIV/AIDS 
prevention, treatment, and related health issues among highly vulnerable youth.  
Proposals in response to this RFA are encouraged to utilize innovative methods 
to design prevention and treatment interventions and to recruit and retain 
highly vulnerable youth participants.  Interventions should be culturally 
relevant and gender sensitive.  Developmental issues of youth and social 
contextual factors that influence drug abuse and HIV/AIDS including gender, 
race, ethnicity, culture, and economic resources should be taken into 
consideration.  Secondary data analysis related to HIV/AIDS and drug use for 
highly vulnerable youth is welcome.  For the purpose of this RFA, youth are 
defined as persons aged 10-24 years.  For research that includes persons 18-24 
that is not youth focused or developmentally sensitive (e.g., interventions 
aimed at adult populations), please refer to NIDA PA “Drug Abuse Aspects of HIV 
and other Infections” 
http://grants.nih.gov/grants/guide/pa-files/PA-04-007.html.

Research Areas

Epidemiology of current and emerging trends related to HIV/AIDS and drug use 
patterns, physical and mental health comorbidities, and social environments of 
highly vulnerable youth, including behaviors associated with HIV exposure.

Children aging into adolescents and adolescents aging into young adults 
represent new cohorts of persons vulnerable to HIV and its consequences.  Many 
of these youth initiated sexual and drug use risk behaviors after the advent of 
HAART.  Changing social contexts, social norms, social policies and new 
technologies can create new vulnerabilities for youth as well as new avenues 
for interventions.  Informed by epidemiological studies, earlier interventions 
may need to be adapted or new interventions developed to reflect current trends 
in sexual and drug use HIV related risk behaviors and social cultural 
influences (e.g., media, including the internet) among sub-populations of 
highly vulnerable youth.   

Illustrative epidemiological research topics include but are not limited to:
   
o   Studies to examine mechanisms underlying risk for groups reporting 
increased HIV infection rates (e.g., youth in the southern U.S., young 
men who have sex with men, particularly young men of color, including 
young Asian and Pacific Islanders).

o   Research on emerging drugs of abuse in relation to HIV risk for highly 
vulnerable youth, including but not limited to club drugs (e.g., ecstasy 
(MDMA), GHB, and ketamine), inhalants, crack cocaine, hallucinogens, 
amphetamines, heroin, potent marijuana and prescription drugs as well as 
access to drugs over the internet.  

o   Research on current youth trends and HIV risk and protective behaviors 
among highly vulnerable youth at-risk for, living with, or affected by 
HIV (e.g., HIV risk associated with tattoos and other body modifications, 
HIV, drug use, and the internet). 

o   Studies to examine longitudinal risk and protective or predictive factors 
for HIV and other infectious diseases in young adulthood for highly 
vulnerable youth.

o   Studies examining drug use, HIV-related risk behaviors, and medical and 
mental health comorbidities including HCV and HBV, especially for youth 
living with HIV and youth affected by HIV.

Development, implementation, evaluation, and dissemination of innovative 
approaches to prevent the transmission of HIV infection 

Evaluations of HIV prevention interventions for youth indicate that theory-
based, model-driven programs can reduce both HIV risk behaviors and relevant 
mediators.  However, these interventions do not fully reduce risk behaviors, 
changes are difficult to sustain over time, many communities have limited 
access to prevention programs, and youth continue to be infected with HIV and 
other blood borne and sexually transmitted pathogens.  Therefore, the 
development of new or adaptation of earlier interventions is needed to reduce 
the drug use related spread of HIV and other infectious diseases.  As noted 
earlier, youth at highest risk experience multiple vulnerabilities.  Effective 
prevention interventions should consider multiple levels of risk (dyadic, 
family, community, structural, in addition to individual).  Since many highly 
vulnerable youth are difficult to reach in traditional intervention settings 
(e.g., school-based programs) research that develops new approaches for 
recruitment and retention including new intervention venues is encouraged.  
Studies that include both behavioral and biological outcomes (e.g., STIs, HCV, 
HBV, and other biomarkers for HIV infection) are also encouraged.    

Illustrative research topics include but are not limited to:

o   Studies on innovative approaches to recruitment and retention to reach 
drug-using youth in venues frequented outside of the school setting 
(e.g., parks, shopping malls, clubs, the internet).

o   Formative research to understand the particular prevention needs of youth 
affected by HIV.

o   Formative research to develop youth-focused and developmentally- 
appropriate interventions with young IDUs including youth initiating drug 
use and/or initiating sexual risk behaviors associated with drug use.

o   Feasibility and acceptability studies of new technologies for highly 
vulnerable youth (e.g., rapid testing). 

o   Research to develop dyadic interventions for highly vulnerable youth 
(e.g., youth involved with partners who engage in high risk HIV/STD-
related behaviors including injection drug use, youth living with HIV and 
their partners).

o   Research to develop appropriate community level interventions to link 
highly vulnerable youth to prevention, treatment, and care services, 
including voluntary counseling and testing for HIV and other infectious 
diseases (e.g., community mobilization, popular opinion leader for 
affected youth, and media, including the internet).

o   Studies on innovative prevention interventions for youth living with HIV.

o   Research on gender-related factors that affect access to and 
effectiveness of HIV prevention interventions.

o   Research on the long-term impact of prevention interventions delivered to 
highly vulnerable youth earlier in life on HIV-related behaviors in 
adolescence and young adulthood. 

Optimizing HIV/AIDS risk reduction through drug abuse treatment 

Drug abuse treatment represents one potentially powerful intervention to reduce 
HIV/AIDS risk among highly vulnerable youth. There is strong, convergent 
evidence that a number of behavioral treatments for adolescent drug abuse 
reduce drug use behavior. Given that drug use is a risk behavior associated 
with HIV directly and indirectly (through other risk behaviors), it is 
reasonable to predict that treatment for adolescent drug abuse can reduce 
HIV/AIDS risk.  While this link has been demonstrated in populations of adult 
drug users, this remains a gap area for youth in drug abuse treatment.  
Research is also lacking regarding how to optimize treatment efficacy in 
reducing both drug use and HIV/AIDS risk behaviors for these populations. 
Please refer to the Behavioral Therapies Development Program Announcement 
(http://grants.nih.gov/grants/guide/pa-files/PA-03-126.html) for more 
information about NIDA’s stage model of research aimed at optimizing behavioral 
treatment. 

Illustrative topics include, but are not limited to:

o   Research to develop and test novel culturally relevant and gender 
sensitive behavioral treatments that address HIV/AIDS risk, including 
research that incorporates knowledge from basic behavioral, affective and 
cognitive science into the development of interventions.

o   Studies to adapt existing treatments to target HIV/AIDS sexual and drug 
use risk reduction.  This includes adapting existing treatments for 
adults to the different social, physiological, cognitive and 
developmental stages of youth.

o   Studies that investigate the mechanisms of action of a behavioral 
treatment’s effect on HIV/AIDS risk.

o   Development of psychometrically sound measures and methods of studying 
HIV/AIDS risk reduction among youth in drug abuse treatment.

Access to, receipt of, and adherence to health and drug treatment services, 
including research on barriers to treatment such as stigma for highly 
vulnerable youth 

Integration of services (e.g., HIV/AIDS medical services with drug abuse 
prevention and/or treatment, HIV/AIDS prevention and treatment services)

There is need for adolescent-specific studies aimed at understanding and 
improving adherence to treatment to minimize the negative physical, 
psychological, cognitive, and social consequences of HIV infection for highly 
vulnerable youth.  Drug abuse and sexual HIV risk behaviors reported by highly 
vulnerable youth can interfere with treatment adherence and utilization and 
negatively impact health.  Youth vulnerable to the consequences of HIV 
infection may face many barriers to accessing treatment including stigma and 
limited opportunities in their communities for health care.  Research is needed 
to develop innovative approaches that improve access to and utilization of 
prevention and treatment services.  Integration of HIV prevention and treatment 
services with other health services including substance abuse treatment may 
improve health outcomes for highly vulnerable youth.

Illustrative topics include, but are not limited to:

o   Research on adherence to treatment for highly vulnerable youth including 
the effect of illicit drug use on adherence to HIV therapy and research 
to develop strategies to enhance adherence to HIV medications among youth 
living with HIV in drug abuse treatment.

o   Research on barriers to accessing treatment at the individual, family, 
community, and policy levels including stigma as well as specific issues 
of HIV infected youth, HIV affected youth, and other groups of highly 
vulnerable youth (e.g., homeless youth, youth involved in the juvenile 
justice system, migrant youth, especially non-English speakers).

o   Development of screening instruments and counseling strategies for early 
diagnosis of HIV and other infectious diseases for youth in drug abuse 
treatment and other healthcare settings.

o   Development of strategies to improve utilization of services by highly 
vulnerable youth.

o   Studies on gender-related factors that affect access to and utilization 
of HIV-related treatment and care.

o   Studies on integration of services (e.g., HIV/AIDS prevention and 
HIV/AIDS treatment, HIV/AIDS prevention/treatment and drug abuse 
prevention/treatment, HIV/AIDS, HBV vaccinations, HCV prevention and drug 
abuse/mental health treatment). 

MECHANISMS OF SUPPORT

This RFA will use the NIH research project (R01), the small grant (R03) and the 
exploratory/development (R21) award mechanisms 
(http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html).  As an applicant 
you will be solely responsible for planning, directing, and executing the 
proposed project.  This RFA is a one-time solicitation.  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 30, 
2004.  Applications supported by NIMH will be funded after October 1, 2004.  
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.  It also uses the modular budgeting 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 budget format.  Otherwise follow the instructions for 
non-modular budget 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.

FUNDS AVAILABLE 

NIDA intends to commit approximately $1,500,000 million in FY 2004 and NIMH 
intends to commit approximately $500,000 in FY 2005 to fund 3 to 7 grants in 
response to this RFA.  An applicant may request for the R01 a project period of 
up to 5 years. For the R03, the project period is 2 years and direct costs up 
to $50,000 for each of those years.  For the R21, the project period is 2 years 
and up to $275,000 in direct costs for the two-year period.  Because the nature 
and scope of the proposed research will vary from application to application, 
it is anticipated that the size and duration of each award will also vary. 
Although the financial plans of NIDA and NIMH 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. 

ELIGIBLE INSTITUTIONS

You may submit (an) application(s) 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 their 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 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 your questions about scientific/research issues to:

Nicolette Borek, Ph.D.
Center on AIDS and Other Medical Consequences of Drug Abuse
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Room 5198, MSC 9555
Bethesda, MD 20892-9555
Telephone: (301) 402-0866
FAX: (301) 594-6566
Email: nborek@nida.nih.gov

Dianne Rausch, Ph.D.
Deputy Director, Center for Mental Health Research on AIDS
National Institute of Mental Health
6001 Executive Blvd., Room 6212, MSC 9619
Bethesda, MD  20892-9619
Telephone: (301) 443-7281
FAX: (301) 443-9719
Email: dr89b@nih.gov

o Direct your questions about peer review issues to:

Teresa Levitin, Ph.D.
Office of Extramural Affairs
National Institute on Drug Abuse/NIH/DHHS
6101 Executive Boulevard, Suite 220, MSC 8401
Bethesda, Maryland 20892-8401
Telephone:  (301) 443-2755
FAX:  (301) 443-0538
Email:  tlevitin@mail.nih.gov

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

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse/NIH/DHHS
6101 Executive Boulevard, Suite 220, MSC 8403
Bethesda, MD  20892-8403
Telephone:  (301) 443-6710
FAX:  (301) 594-6849
Email:  gf6s@nih.gov

Mr. Brian Albertini
Grants Management Branch 
National Institute of Mental Health 
6001 Executive Blvd., Room 6115
Bethesda, MD 20892
Telephone: (301) 443-0004
Fax: (301) 443-0219
Email: albertib2@mail.nih.gov

LETTER OF INTENT
 
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 NIDA staff to estimate the potential review workload and plan the 
review.
 
The letter of intent is to be sent by the date listed at the beginning of this 
document.  The letter of intent should be sent to:

Director
Office of Extramural Affairs
National Institute on Drug Abuse/NIH/DHHS
6101 Executive Boulevard, Suite 234, MSC 8401
Bethesda, MD  20892-8401
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 443-2755
FAX:  (301) 443-0538
Email:  tlevitin@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 document 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.

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.

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: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the 
application, including the Checklist, and three signed, photocopies, in one 
package to:
 
Center For Scientific Review
National Institutes Of Health/DHHS
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 and all 
copies of the appendix material must be sent to:

Director
Office of Extramural Affairs
National Institute on Drug Abuse/NIH/DHHS
6101 Executive Boulevard, Suite 220, MSC 8401
Bethesda, MD  20892-8401
Rockville, MD  20852 (for express/courier service)

APPLICATION PROCESSING: Applications must be received on or before 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.

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignments within 8 weeks.

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 unfounded 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.  

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by NIDA.  Incomplete applications will not be reviewed.  If the 
application is not responsive to the RFA, NIH staff may contact the applicant 
to determine whether to return the application to the applicant or submit it 
for review in competition with unsolicited applications at the next appropriate 
NIH review cycle.
 
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 
NIDA 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 Advisory Council on Drug Abuse 
or the National Advisory Mental Health Council.

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 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.

(1) SIGNIFICANCE:  Please assess the extent to which the study aims are 
consistent with the goals of the RFA. 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?  Does the study address an important 
problem consistent with the goals of this RFA?

(2) 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?

(3) 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?

(4) 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)?

(5) 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. (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.  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

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

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:    February 17, 2004 
Application Receipt Date:         March 17, 2004
Peer Review Date:                 June/July 2004
Council Review:                   September 2004
Earliest Anticipated Start Date:  September 30, 2004

AWARD CRITERIA

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.

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 SAFETY AND 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. 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 Safety and Monitoring, NIH Guide for Grants 
and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

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 AMENDMENT "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 are 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. 
This policy applies to all initial (Type 1) applications submitted for receipt 
dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that 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.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on 
hESCs can be found at http://stemcells.nih.gov/index.asp and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide, in the project 
description and elsewhere in the application as appropriate, the official NIH 
identifier(s) for the hESC line(s)to be used in the proposed research.  
Applications that do not provide this information will be returned without 
review. 

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). 
Those who must comply with the Privacy Rule (classified under the Rule as 
“covered entities”) must do so by April 14, 2003 (with the exception of small 
health plans which have an extra year to comply).  

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.

HIV/AIDS COUNSELING AND TESTING POLICY FOR THE NATIONAL INSTITUTE ON DRUG 
ABUSE:  Researchers funded by NIDA who are conducting research in community 
outreach settings, clinical, hospital settings, or clinical laboratories and 
have ongoing contact with clients at risk for HIV infection, are strongly 
encouraged to provide HIV risk reduction education and counseling.  HIV 
counseling should include offering HIV testing available on-site or by referral 
to other HIV testing service for persons at risk for HIV infection including 
injecting drug users, crack cocaine users, and sexually active drug users and 
their sexual partners.  For more information see 
http://grants.nih.gov/grants/guide/notice-files/NOT-DA-01-001.html.

NATIONAL ADVISORY COUNCIL ON DRUG ABUSE RECOMMENDED GUIDELINES FOR THE 
ADMINISTRATION OF DRUGS TO HUMAN SUBJECTS:  The National Advisory Council on 
Drug Abuse recognizes the importance of research involving the administration 
of drugs to human subjects and has developed guidelines relevant to such 
research.   Potential applicants are encouraged to obtain and review these 
recommendations of Council before submitting an application that will 
administer compounds to human subjects.  The guidelines are available on NIDA's 
Home Page at http://www.nida.nih.gov under the Funding, or may be obtained by 
calling (301) 443-2755.

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 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.

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