This Program Announcement expires on November 30, 2004 unless reissued.

STATISTICAL METHODS IN HIV/AIDS RESEARCH

Release Date:  November 29, 2001 

PA NUMBER:  PA-02-024 (see amendment NOT-AI-04-038)

National Institute of Allergy and Infectious Diseases
National Institute of Mental Health

THIS PA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  MODULAR 
INSTRUCTIONS MUST BE USED FOR RESEARCH GRANT APPLICATIONS UP TO 
$250,000 PER YEAR. MODULAR BUDGET INSTRUCTIONS ARE PROVIDED IN SECTION 
C OF THE PHS 398 (REVISION 5/2001) AVAILABLE AT 
http://grants.nih.gov/grants/funding/phs398/phs398.html.  

PURPOSE

The National Institute of Allergy and Infectious Diseases (NIAID), and 
the National Institute of Mental Health (NIMH), National Institutes of 
Health (NIH), invite applications for the development of original 
statistical methods to advance the understanding, treatment, and 
prevention of human
immunodeficiency virus (HIV) disease/AIDS.

NIH Support of Research on this Topic

Although this Program Announcement is being issued by NIAID and NIMH, 
the other components of NIH listed below also have an interest in and 
support research on the topics covered. Applicants may wish to contact 
each of these NIH components listed in INQUIRIES to find out about other 
funding opportunities.  Institutes and Centers at NIH use different 
grant mechanisms to support their portfolio of research; the components 
listed here may not use all of the mechanisms specified for this Program 
Announcement.

NCRR:   Mathematical models of basic biological processes.
NCI:    Epidemiology of AIDS/retroviral-associated cancers.
NICHD:  Statistical methods and designs for analyzing the determinants 
of sexual behavior related to HIV risk and the impact of interventions 
to modify sexual behavior, including techniques to improve the accuracy 
of self-report data; demographic approaches to modeling the spread and 
impact of HIV within the population.
NIDA:   Mathematical models of transmission related to drug abuse and 
effects of behavioral prevention programs.

Applications submitted in response to Program Announcements are assigned 
according to established PHS referral guidelines.  When the subject of 
an application is of interest to more than one component of NIH, dual 
assignments are made.

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 Program 
Announcement (PA), "Statistical Methods in HIV/AIDS Research", is 
related to the priority areas of HIV infection, sexually transmitted 
diseases, immunization and infectious diseases, and surveillance and 
data systems. Potential applicants may obtain a copy of "Healthy People 
2010" at http://www.health.gov/healthypeople/.

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

This PA will use the National Institutes of Health (NIH) research 
project grant (R01 and R03) award mechanisms. Responsibility for the 
planning, direction, and execution of the proposed project will be 
solely that of the applicant. The total project period for an 
application submitted in response to this PA may not exceed 5 years.

Specific application instructions have been modified to reflect "MODULAR 
GRANT" and "JUST-IN-TIME" streamlining efforts that have been adopted by 
the NIH. Complete and detailed instructions and information on Modular 
Grant applications have been incorporated into the PHS 398 (rev. 5/01). 
Additional information on Modular Grants can be found at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

A notice of modification and update (OD-00-046) regarding modular 
grants was released on 7/24/00 and can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-046.html.

RESEARCH OBJECTIVES

Background

The AIDS epidemic has posed unique challenges for the design of 
therapeutic and prevention trials, and epidemiologic and basic science 
studies, and for the analysis of data resulting from each of these. New 
statistical methods have been developed to handle such problems as the 
tracking and prediction of number of AIDS cases, the use and assessment 
of immunologic and virologic measurements, and the analysis and 
monitoring of clinical trials with censored and missing data. Recent 
years have seen an increasing array of available drugs, diversity of 
affected populations and viral characteristics, and an increased 
appreciation of the dynamic, multivariate, and multiphasic nature of HIV 
disease. Research in this changing and ever more complex environment 
presents great methodological challenges.

Research Objectives and Scope

Innovative statistical methods are expected to continue to play an 
important role in the investigation of new AIDS therapies and prevention 
strategies.  Such methods need to be attuned to the particular features 
of HIV/AIDS biology and epidemiology.  The evolving circumstances of the 
epidemic and the expanding set of research tools also need to be 
considered.  For instance, new and improved statistical methods are 
needed for the effective utilization of immunologic and virologic 
measures, for explaining the relationship between surrogate markers and 
clinical outcomes and for making decisions on when to start and switch 
treatment. Developments of such statistical methods provide new 
approaches for evaluation of HIV therapies and vaccines, and the study 
of HIV transmission and pathogenesis. NIH guidelines for the use of 
antiretroviral agents provide a backdrop for the design of ethical 
clinical and prevention trials, but questions remain in the use of 
highly, though not universally, effective treatment regimens.  Little is 
known, for instance, on how to optimally use virologic and other 
laboratory measures in decisions about when to start and when to switch 
therapy and the sequence of regimens.  The appropriate and efficient 
utilization of multiple endpoints, clinical as well as laboratory, in 
efficacy studies needs further consideration.  Mathematical models have 
provided some clues for effective treatment strategies, but further 
development is required to capture enough features of disease dynamics 
to produce reliable and relevant inferences.

The areas of research listed below are not all-inclusive, but are 
intended to provide guidance as to the types of research that are of 
interest.

1. Design and analysis of novel clinical trials involving, for example, 
multiple or combined endpoints, treatment changes or multicomponent 
treatment strategies, or sequential evaluation of therapies 

2. Trial designs for the evaluation of HIV vaccine candidates and other 
interventions such as STD diagnosis and treatment, behavioral 
counseling, microbicides, chemoprophylactic agents, and antiretroviral 
therapy which assess the indirect as well as direct effects of 
intervention 

3. Statistical methods for assessing the impact of HIV genetic and 
antigenic variation on the effectiveness of HIV vaccines 

4. Design and analysis of explanatory clinical studies, for example, 
nested studies within clinical trials to explore questions regarding HIV 
pathogenesis or to assess the validity of biological markers such as 
viral load as surrogate endpoints 

5. Statistical methods to assess the timing and correlates of HIV 
perinatal transmission and to address unique features of pediatric HIV 
disease 

6. Design and analysis of early stage therapy studies (including 
preclinical studies and Phase I and II clinical trials) for the 
efficient screening and evaluation of drugs, drug combinations, or doses 

7. Mathematical or statistical modeling of HIV pathogenesis including 
acute infection, resistance, interactions among multiple pathogens, and 
the course of HIV disease 

8. Mathematical or statistical modeling of the potential population-
level effects of HIV vaccination programs and other prevention 
strategies on the control of HIV transmission 

9. Design of animal challenge studies for assessing the effects of HIV 
(or analogous) vaccines and chemoprophylactic strategies 

10. Methods for the statistical evaluation of data quality in large, 
multicentered clinical trials 

11. Mathematical or statistical modeling of HIV transmission and spread 
within at-risk populations 

12. Design and analysis of Phase I and II safety and immunogenicity 
studies of HIV vaccine candidates 

13. Improved methods for obtaining self-report data and use of multiple 
methods (e.g., behavioral and biological) to establish psychometrics 

14. Improved methods for assessing family systems and social networks, 
and data analysis strategies for multiple data points in longitudinal 
studies of family and social systems 

15. Mathematical models using available seroincidence data for linking 
behavioral change with reduction in HIV transmission at different levels 
of seroprevalence and social mixing 

To address these issues, a multidisciplinary approach is strongly 
encouraged. The mathematical/statistical modeling of the potential 
impact of HIV vaccination, for example, would benefit from a research 
team, which includes persons with expertise in demography, STD control, 
behavioral science, and vaccine development, in addition to statistics 
and/or mathematics.

TERMS AND CONDITIONS OF AWARD

When clinical studies or trials are a component of the research 
proposed, NIAID policy requires that studies be monitored commensurate 
with the degree of potential risk to study subjects and the complexity 
of the study. Terms and Conditions of Award will be included with 
awards. NIAID policy was announced in the NIH Guide on February 24, 
2000 and is available at:  
http://grants.nih.gov/grants/guide/notice-files/NOT-AI-00-003.html.  
The full policy including terms and conditions of award is available at:  
http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf

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 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

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 the policy.

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. Reviewers are cautioned that 
their anonymity may be compromised when they directly access an 
Internet site.

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 the following website: 
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.

APPLICATION PROCEDURES

The PHS 398 research grant application instructions and forms (rev. 
5/01) at http://grants.nih.gov/grants/forms.htm must be used in applying 
for these grants and will be accepted at the standard application 
deadlines (http://grants.nih.gov/grants/dates.htm) as indicated in the 
application kit. This version of the PHS 398 is available in an 
interactive, searchable format.  For further assistance contact 
GrantsInfo, Telephone 301/435-0714, Email: GrantsInfo@nih.gov.

Applicants planning to submit an investigator-initiated new (type 1), 
competing continuation (type 2), competing supplement, or any amended 
or revised version of the preceding grant application types requesting 
$500,000 or more in direct costs for any year are advised that he or 
she must contact the Institute or Center (IC) program staff before 
submitting the application, i.e., as plans for the study are being 
developed. Furthermore, the application must obtain agreement from the 
IC staff that the IC will accept the application for consideration for 
award. Finally, the applicant must identify, in a cover letter sent 
with the application, the staff member and Institute or Center who 
agreed to accept assignment of the application. 

This policy requires an applicant to obtain agreement for acceptance of 
both any such application and any such subsequent amendment. Refer to 
the NIH Guide for Grants and Contracts, March 20, 1998 at 
http://grants.nih.gov/grants/guide/notice-files/not98-030.html

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS
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 NIH staff.  The research grant 
application form PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html is to be used 
in applying for these grants, with modular budget instructions provided 
in Section C of the application instructions.  

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

Submit a signed, typewritten original of the application, including the 
Checklist, and 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)

REVIEW CONSIDERATIONS

Applications will be assigned on the basis of established NIH referral 
guidelines. Applications will be evaluated for scientific and technical 
merit by an appropriate scientific review group convened in accordance 
with the standard NIH peer review procedures. As part of the initial 
merit review, all applications will 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 applications under 
review, will be discussed, assigned a priority score, and 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 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. 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: 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 
method? 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:

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

o The reasonableness of the requested budget and the requested period 
of support as it relates to the proposed research

o 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.

AWARD CRITERIA

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

o scientific merit (as determined by peer review)
o availability of funds
o programmatic priorities

INQUIRIES

Inquiries are encouraged. The opportunity to clarify any issues or 
questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Misrak Gezmu, Ph.D. 
Division of AIDS
National Institute of Allergy and Infectious Diseases 
Room Number 4242, MSC-7620
6700-B Rockledge Drive
Bethesda, MD  20892-7620 
Telephone:  (301) 435-3722 
FAX:  (301) 402-0145 
Email:  mailto:mgezmu@niaid.nih.gov 

Willo Pequegnat, Ph.D.
Office on AIDS Research
National Institute of Mental Health
Parklawn Building, Room 18-101
Rockville, MD  20857
Telephone:  (301) 443-6100
FAX:  (301) 443-9719
Email:  WPEQUEGN@nih.gov

Direct inquiries regarding fiscal matters to

Mary Ledford
Grants Management Branch
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4B24
Bethesda, MD  20892-7610
Telephone:  (301) 402-6446
FAX:  (301) 480-3780
Email:  ml28g@nih.gov

Other NIH Institutes and Centers with related research interests:
Christine A. Bachrach, Ph.D.
Center for Population Research
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8B13
Bethesda, MD  20892-7510
Telephone:  (301) 496-1174
FAX:  (301) 496-0962
Email:  cbachrach@nih.gov

Vaurice Starks, M.S.
Analytic Epidemiology Research Branch
Division of Cancer Control and Population Sciences
Executive Plaza North, Room 5103
6130 Executive Blvd. MSC 7324
Bethesda, MD  20892-7395
Telephone:  (301) 402-9375
FAX:  (301) 402-4279
Email:  vs38j@nih.gov

Dr. Peter I. Hartsock
Center on AIDS and Other Medical Consequences of Drug Abuse
National Institute on Drug Abuse
National Institutes of Health
6001 Executive Boulevard, Room 5198 
Bethesda, MD  20892-9593
Phone:  (301) 402-1964
Fax:  (301) 480-4544
email:  ph45z@nih.gov
 
Michael C. Chang, Ph.D.
Comparative Medicine
National Center for Research Resources
National Institutes of Health
One Rockledge Center, Room 6174
6705 Rockledge Drive
Bethesda, MD  20892
Telephone: (301) 435-0744
FAX:  (301) 480-3819
Email:  ChangM@NCRR.NIH.GOV

AUTHORITY AND REGULATIONS 

This program is described in the Catalogue of Federal Domestic 
Assistance in the following citations: No. 93.855, Immunology, Allergy, 
and Transplantation Research and No. 93.856, Microbiology and 
Infectious Diseases Research. Awards are made under authorization of 
Sections 301 and 405 of the Public Health Service Act as amended (42 
USC 241 and 284) and administered under NIH grants policies and Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. This program is not 
subject to the intergovernmental review requirements of Executive Order 
12372 or Health Systems Agency review.

The NIH Grants Policy Statement is available at 
http://grants.nih.gov/grants/policy/policy.htm.  This document includes 
general information about the grant application and review process; 
information on the terms and conditions that apply to NIH Grants and 
cooperative agreements; and a listing of pertinent offices and 
officials at the NIH.

The PHS strongly encourages all grant and contract 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, and 
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.


Return to Volume Index

Return to NIH Guide Main Index


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.