VIRAL HEPATITIS AND HIV IN DRUG AND ALCOHOL USERS

Release Date:  January 11, 2000

RFA:  DA-00-006

National Institute on Drug Abuse
National Institute on Alcohol Abuse and Alcoholism

Letter of Intent Receipt Date:  February 28, 2000
Application Receipt Date:       March 28, 2000

THIS REQUEST FOR APPLICATIONS (RFA) USES THE “MODULAR GRANT” AND “JUST-
IN-TIME” CONCEPTS.  IT INCLUDES DETAILED MODIFICATIONS TO STANDARD 
APPLICATION INSTRUCTIONS THAT MUST BE USED WHEN PREPARING APPLICATIONS 
IN RESPONSE TO THIS RFA.

PURPOSE 

The National Institute on Drug Abuse (NIDA) and the National Institute 
on Alcohol Abuse and Alcoholism invite applications for cross-
disciplinary research on viral hepatitis and HIV/AIDS in drug and/or 
alcohol users.  This RFA is intended to address gaps in prevention, 
natural history, pathogenesis, and treatment research related to viral 
hepatitis infection in drug  and/or alcohol users, both with and without 
concomitant HIV infection, with an emphasis on research related to co-
infections. Epidemiologic studies demonstrate that hepatitis C (HCV) and 
hepatitis B (HBV) are endemic among injection drug users (IDUs), as well 
as those that abuse alcohol. Common risk factors in drug users,, such as 
multi-person use of syringes, have resulted in high prevalence rates for 
HCV, HBV, and the human immunodeficiency virus (HIV) infection.  
Improved approaches to prevent acquisition and ongoing transmission of 
infection are urgently needed, as are strategies to improve access to 
diagnostic screening and care.  Factors determining progression and 
outcome in drug users infected with HCV are not well understood, nor are 
the consequences of concomitant infections and ongoing drug use.  Few 
data are available regarding the effectiveness of behavioral and 
biomedical interventions in drug users.  In HIV-HCV co-infected 
individuals, there is increasing evidence that HIV seropositivity 
accelerates HCV-related liver fibrosis progression.  Alcohol consumption 
in this population increases the risk of progression to end-stage liver 
disease.

This RFA will support epidemiologic, prevention, clinical and basic 
research on the acquisition and transmission of infection; on the 
clinical course and consequences of infection; and on 
the design and effectiveness of behavioral and medical interventions for 
reducing risk behaviors, disease transmission, morbidity and mortality. 
Researchers are encouraged to utilize and integrate complementary 
methodological approaches in their study designs, including 
epidemiology, ethnography, prevention science, virology, and clinical 
medicine.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of “Healthy People 2000,” a 
PHS-led national activity for setting priority areas.  This RFA, “Viral 
Hepatitis and HIV in Drug and Alcohol Users,” is related to the priority 
areas of alcohol and other drugs, HIV infection, and sexually 
transmitted diseases.  Potential applicants may obtain a copy of 
“Healthy People 2000” at 
http://odphp.osophs.dhhs.gov/pubs/hp2000.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign for-profit and 
non-profit organizations, public and private, such as universities, 
colleges, hospitals, laboratories, units of state and local governments, 
and eligible agencies of the federal government.  Racial/ethnic minority 
individuals, women, and persons with disabilities are encouraged to 
apply as Principal 
Investigators.  

MECHANISM OF SUPPORT

The mechanism of support for this RFA will be the investigator-initiated 
research project grant (R01). Applicants are advised to contact NIDA or 
NIAAA program staff listed under INQUIRIES for additional information.  
Responsibility for the planning, direction, and execution of the 
proposed project will be solely that of the applicant.  Specific 
information on individual research mechanisms can be obtained from the 
NIDA home page at 
http://www.nida.nih.gov/Funding.html.

Support may be requested for a period of up to 5 years for R01 grants.  
Modular budgeting procedures apply for grants up to $250,000.  See 
http://grants.nih.gov/grants/funding/modular/modular.htm for further 
information about modular budgets. 

FUNDS AVAILABLE

NIDA intends to commit approximately $1,500,000 in FY 2000 to fund 
approximately four to five new grants in response to this RFA. NIAAA 
intends to commit approximately $1,000,000 to fund approximately three 
to four new grants. Because the nature and scope of the research 
proposed may vary, it is anticipated that the size of each award will 
also vary. Although the financial plans of NIDA and NIAAA provide 
support for this program, awards pursuant to this RFA are contingent 
upon the availability of funds and the receipt of a sufficient number of 
applications of outstanding scientific and technical merit.

RESEARCH OBJECTIVES

Background

Research in both domestic and international populations of IDUs has 
demonstrated consistently high rates of HCV infection, and IDUs account 
for the majority of incident HCV cases acquired annually in the United 
States.  Studies also demonstrate high incidence and prevalence rates 
for HBV infection in IDUs. Research has shown that acquisition of HBV 
and HCV can occur rapidly following initiation of injection drug use, 
with very high rates of new HBV and HCV infection occurring among new 
injectors within the first year of injection. Co-infection rates for 
HBV, HCV, and HIV tend to cluster among IDUs and are characteristically 
endemic among experienced IDUs. Research has also revealed a higher risk 
of HIV and HCV maternal-to-infant transmission from mothers who are co-
infected with both viruses.  While studies have established that the 
major mode of acquisition of hepatitis in drug users is through 
parenteral drug use, the roles of non-parenteral drug use and high-risk 
sexual behavior in the acquisition and transmission of HCV are poorly 
understood.  

Epidemiologic data highlight a need for prevention research that targets 
at-risk groups of adolescents and young adults, non-injecting drug 
users, non-injectors transitioning to injecting drug use, persons who 
have initiated drug injection, and experienced injectors. Comprehensive 
intervention approaches to improve access to infection screening and HBV 
immunization to prevent ongoing transmission from already infected drug 
users and to reduce 
morbidity associated with continued drug and alcohol use are critical.  
Research gaps remain in understanding the pathogenesis of multiple viral 
infections, the impact of drug or alcohol use and other factors on 
disease progression, and the clinical consequences of infection in drug 
and/or alcohol users with multiple acute and chronic health conditions.  
Given the large population of drug and/or alcohol users infected with 
both hepatitis and HIV, there is a need for initiating studies to 
address treatment issues for drug and/or alcohol users with both single 
and concomitant infections.  Few data are available regarding 
therapeutic effectiveness, hepatotoxicity, drug interactions, and 
clinical outcomes.

Areas of Research Focus
 
This initiative will support research in the following areas: (1) the 
epidemiology of acquisition and transmission of single and co-occurring 
blood-borne infections; 2) the behavioral dynamics and drug use-related 
processes associated with the acquisition and transmission of viral 
hepatitis and HIV infections, including factors which influence 
transitions from non-injection to injection drug use and their 
implications for the development of prevention interventions; (3) the 
adaptation, replication, and testing of community-based outreach 
prevention interventions to extend the lessons learned from HIV 
intervention research in preventing the spread and co-occurrence of HIV, 
HBV, HCV; (4) the impact of syringe access and needle exchange programs 
on the incidence, prevalence, and transmission of viral 
hepatitis and HIV infections, and as points of access to facilitate 
entry to drug treatment and ancillary social, health, and medical 
services; (5) the natural history of single and co-occurring blood-borne 
infections, in both acute and chronic infection; (6) the viral, 
immunologic, genetic, and drug/alcohol use factors which may influence 
susceptibility, recovery and persistence, and progression of one or more 
viral diseases; (7) the association of viral loads and viral load 
fluctuations relative to demographic characteristics, sexual 
and drug/alcohol using behaviors, and HIV virologic and immunologic 
status; (8) the social, behavioral, and medical consequences of viral 
hepatitis and HIV for drug and/or alcohol users; (9) the strategies for 
improving access to and delivery of biomedical interventions to drug 
users, such as HBV vaccines, available therapeutic agents, and 
screening/testing and counseling services; (10) the effectiveness of 
biomedical interventions, the consequences (e.g., drug interactions, 
hepatotoxicity) of multiple therapeutic interventions, and the 
development of improved clinical management approaches; (11) the 
bioethical considerations involving availability of care to drug users 
and provider attitudes regarding the inclusion of drug users in research 
and in clinical management approaches; and (12) the role of alcohol use 
in the progression of liver fibrosis to end-stage liver disease in 
individuals with HCV-HIV co-infection. 

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

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

All investigators proposing research involving human subjects should 
read the “NIH Guidelines for Inclusion of Women and Minorities as 
Subjects in Clinical Research,” published in the Federal Register on 
March 28, 1994 (FR 59 14508-14513) and in the NIH Guide for Grants and 
Contracts, Volume 23, Number 11, March 18, 1994, available on the web 
at:  
http://grants.nih.gov/grants/guide/notice-files/not94-100.html.

NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS 
IN RESEARCH INVOLVING HUMAN SUBJECTS:

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

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

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

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/ or may be obtained by calling (301) 
443-2755.

LETTER OF INTENT

Prospective applicants are asked to submit by February 28, 2000, a 
letter of intent that includes a descriptive title of the proposed 
research; the name, address, telephone number, and institution of the 
Principal Investigator; the names of other key investigators and their 
respective institutions (if applicable); and the title and number of 
this RFA in response to which the application will be submitted.  
Although a letter of intent is not required, is not binding and is not a 
factor in the peer review of the application, the information it 
contains is helpful in planning for the review of applications.

The letter of intent is to be sent to:

Director, Office of Extramural Affairs
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD  20892-9547
Telephone:  (301) 443-2755
FAX:  (301) 443-0538

APPLICATION PROCEDURES

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

SPECIFIC APPLICATION INSTRUCTIONS FOR MODULAR GRANTS

The modular grant concept establishes specific modules in which direct 
costs may be requested, as well as a maximum level for requested 
budgets.  Only limited budgetary information is required under this 
approach.  The just-in-time concept allows applicants to submit certain 
information only when there is a possibility for an award.  It is 
anticipated that these changes will reduce the administrative burden for 
the applicants, reviewers, and Institute staff.  The research grant 
application form PHS 398 (rev. 4/98) is to be used in applying for these 
grants, with the modifications noted below.

BUDGET INSTRUCTIONS

Modular Grant applications will request direct costs in $25,000 modules, 
up to a total direct cost request of $250,000 per year.  (Applications 
that request more than $250,000 direct costs in any year must follow the 
traditional PHS 398 application instructions.)  The total direct costs 
must be requested in accordance with the program guidelines and the 
modifications made to the standard  PHS 398 application instructions 
described below:

PHS 398

FACE PAGE - Items 7a and 7b should be completed, indicating Direct Costs 
(in $25,000 increments up to a maximum of $250,000) and Total Costs 
[Modular Total Direct plus Facilities and Administrative  (F&A) costs] 
for the initial budget period. Items 8a and 8b should be completed 
indicating the Direct and Total Costs for the entire proposed period of 
support.

DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form 
Page 4 of the PHS 398.  It is not required and will not be accepted with 
the application.

BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete the 
categorical budget table on Form Page 5 of the PHS 398.  It is not 
required and will not be accepted with the application.

NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget 
Narrative page (see 
http://grants.nih.gov/grants/funding/modular/modular.htm for sample 
pages).  At the top of the page, enter the total Direct Costs requested 
for each year.  This is not a Form page.

Under Personnel, list key project personnel, including their names, 
percent of effort, and roles on the project.  No individual salary 
information should be provided.  However, the applicant should use the 
NIH appropriation language salary cap and the NIH policy for graduate 
student compensation in developing the budget request.

For Consortium/Contractual costs, provide an estimate of total costs 
(Direct plus F&A) for each year, each rounded to the nearest $1,000.  
List the individuals/organizations with whom consortium or contractual 
arrangements have been made, the percent effort of key personnel, and 
the role on the project.  Indicate whether the collaborating institution 
is foreign or domestic.  The total cost for a consortium/contractual 
arrangement is included in the overall requested Modular Direct Cost 
amount.  Include the letter of intent to establish a consortium.

Provide an additional narrative budget justification for any variation 
in the number of modules requested.

BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used 
by reviewers in the assessment of each individual's qualifications for a 
specific role in the proposed project, as well as to evaluate the 
overall qualifications of the research team.  A biographical sketch is 
required for all key personnel, following the instructions below.  No 
more than three pages may be used for each person.  A sample 
biographical sketch may be viewed at:  
http://grants.nih.gov/grants/funding/modular/modular.htm.

- Complete the educational block at the top of the Form page;
- List position(s) and any honors;
- Provide information, including overall goals and responsibilities, on 
research projects ongoing or completed during the last three years; and
- List selected peer-reviewed publications, with full citations.

CHECKLIST - This page should be completed and submitted with the 
application.  If the F&A rate agreement has been established, indicate 
the type of agreement and the date.  All appropriate exclusions must be 
applied in the calculation of the F&A costs for the initial budget 
period and all future budget years.

The applicant should provide the name and phone number of the individual 
to contact concerning fiscal and administrative issues if additional 
information is necessary following the initial review. 

The RFA label available in the PHS 398 (rev. 4/98) application form must 
be affixed to the bottom of the face page of the application.  Failure 
to use this label could result in delayed processing of the application 
such that it may not reach the review committee in time for review.

In addition, the title and number of this RFA must be typed in Item 2 on 
the face page of the application form, and the YES box must be marked.  
The RFA number must be typed on the label as well.

The sample RFA label is available at  
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf and has been 
modified to allow for this change.  Please note this is in pdf format.

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
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

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

Director, Office of Extramural Affairs
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD  20892-9547
Rockville, MD  20852 (for express/courier service)

Applications must be received by March 28, 2000.  If an application is 
received after that date, it will be returned to the applicant without 
review.  The Center for Scientific Research (CSR) will not accept any 
application in response to this RFA that is essentially the same as one 
currently pending initial review, unless the applicant withdraws the 
pending application.  The CSR will not accept any application that is 
essentially the same as one already reviewed.  This does not preclude 
the submission of substantial revisions of applications already 
reviewed, but such applications must include an introduction addressing 
the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR 
and for responsiveness by NIDA.  Incomplete and/or non-responsive 
applications will be returned to the applicant without further 
consideration.

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, a process will be 
used by the initial review group in which applications receive a written 
critique and 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, assigned a priority score, 
and receive a second level review by the National Advisory Council on 
Drug Abuse or the National Advisory Council on Alcohol Abuse and 
Alcoholism.

REVIEW CRITERIA

The goals of NIH-supported research are to advance the understanding of 
biological systems, improve the control of disease, and enhance health.  
In the written comments, reviewers will be asked to discuss the 
following aspects of the application in order to judge the likelihood 
that the proposed research will have a substantial impact on the pursuit 
of these goals.  Each of these criteria will be addressed and considered 
in assigning the overall score, weighting them as appropriate for each 
application.  Note that the application does not need to be strong in 
all categories to be judged likely to have major scientific impact and 
thus deserve a high priority score.

(1)  Significance:   Are the goals and objectives of this application 
relevant to this 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?  

(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?

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

The adequacy of plans to include both genders, minorities, and their 
subgroups, as appropriate for the scientific goals of the research.  
Plans for the recruitment and retention of subjects will also be 
evaluated. 

The adequacy of plans to make data available to other investigators in a 
timely fashion.

The reasonableness of the proposed budget and duration in relation to 
the proposed research.

The adequacy of the proposed protection for humans, animals, or the 
environment, to the extent they may be adversely affected by the project 
proposed in the application.

The adequacy of plans for including children as appropriate for the 
scientific goals of the research.

Schedule:
Letter of Intent:          February 28, 2000		
Application Receipt Date:  March 28, 2000
Council Review:            September 2000			
Earliest Start Date:       September 29, 2000		

AWARD CRITERIA

Award criteria that will be used to make award decisions include:  
scientific merit as determined by peer review, availability of funds, 
and programmatic priorities.

INQUIRIES

Inquiries concerning this RFA are strongly encouraged.  The opportunity 
to clarify issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Elizabeth Lambert, M.S.
Center on AIDS and Other Medical Consequences of Drug Abuse 
National Institute on Drug Abuse
6001 Executive Boulevard, Room 5198, MSC 9593
Bethesda, MD 20892-9593
Telephone :  (301) 402-1933
FAX :  (301) 443-4100
E-mail: el46i@nih.gov  

Thomas F. Kresina, Ph.D.
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Room 402, MSC 7003
Bethesda, MD  20892-7003
Telephone:  (301) 443-6537
FAX (301) 594-0673
E-mail: tk13v@nih.gov

Direct inquiries regarding fiscal matters to:

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3131, MSC 9541
Bethesda, MD  20892-9541
Telephone:  (301) 443-6710
FAX :  (301) 594-6847
E-mail: gf6s@nih.gov

Nancy Brennan		
Budget Officer		
National Institute on Alcohol Abuse and Alcoholism
PFMB		
Willco Bldg, Suite 412		
6000 Executive Boulevard	
Bethesda, MD 20892-7003	
Telephone:  (301) 443-9735
FAX: (301) 443-8634
E-mail: nbrennan@wilco.niaaa.nih.gov

Direct inquiries regarding review matters to:

Teresa Levitin, Ph.D.
Director
Office of Extramural Affairs
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD  20892-9547
Telephone :  (301) 443-2755
FAX:  (301) 443-0538
E-mail:  tl25u@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance 
No. 93.279.  Awards are made under authorization of the Public Health 
Service Act, Title IV, Part A (Public Law78-410, as amended by Public 
Law 99-158, 42 USC 241 and 285) and are administered under PHS grants 
policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74.  This 
program is not subject to the intergovernmental review requirements of 
Executive Order 12372 or Health Systems Agency review.

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


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