MOLECULAR MARKERS AND MECHANISMS OF HIV-ASSOCIATED DEMENTIA

RELEASE DATE:  March 12, 2004

RFA Number:  RFA-MH-05-002 (see addendum NOT-MH-04-004)

EXPIRATION DATE:  May 12, 2004 

Department of Health and Human Services (DHHS)

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

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

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBERS:  93.242, 93.279

LETTER OF INTENT RECEIPT DATE:  April 12, 2004
APPLICATION RECEIPT DATE:  May 11, 2004  

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o  Purpose of this RFA
o  Research Objectives
o  Mechanism(s) 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 of Mental Health (NIMH) and the National Institute on Drug 
Abuse (NIDA) invite applications proposing to identify and characterize novel 
molecular and genetic markers associated with distinct stages of progression of 
HIV-associated nervous system disease in the context of highly active anti-
retroviral therapy (HAART).  Research on the role of unique molecular and genetic 
markers in defining mechanisms of neuropathogenesis, host genetic susceptibility to 
development of central nervous system (CNS) disease and response to treatment are 
also important areas of focus of this Request for Applications (RFA).  The use of 
state-of-the-art microarray technology, proteomics, molecular genetics, and 
neuroimaging techniques to define and characterize novel molecular and genetic 
markers associated with HIV-induced nervous system disease are encouraged.

RESEARCH OBJECTIVES

The introduction of HAART has resulted in significantly improved survival of AIDS 
patients and decreased incidence of HIV-associated dementia (HAD).  HAD is 
estimated to constitute about 5% of new AIDS-defining illnesses in the USA.  
Although HAART has resulted in a decline in the incidence of HIV dementia, the 
improved survival has resulted in increased cumulative prevalence of nervous system 
complications of AIDS.  HAART does not provide full protection against neurological 
damage in HIV/AIDS in part, because the blood-brain barrier is only partially 
permeable to anti-retroviral agents.  The frequency of HIV-associated encephalitis 
observed in post-mortem tissue has remained constant, suggesting that HAART does 
not eliminate HIV-1 infection in the central nervous system.  Furthermore, while 
improvements in treatment for AIDS have occurred in the developed world, a 
significant number of new infections are being reported in the developing countries 
including China, India, Eastern Europe, and Sub Saharan Africa.  The neurologic and 
neuropsychiatric complications resulting from new infections in the developing 
world are likely to cause significant morbidity and mortality.

Extensive research is underway to better understand the underlying mechanisms of 
neuropathogenesis of HIV-1.  Currently there is limited consensus on the pathways 
leading to neurologic and neuropsychiatric disease in the setting of HAART.  While 
HAART has resulted in increased prevalence of HIV dementia, the neurologic disease 
has been reported to be milder.  It has been suggested that in the era of HAART, 
distinct subtypes of HAD are observed. The proposed subtypes include the following:  
a) subacute progressive dementia; b) chronic active dementia; and c) chronic 
inactive dementia.

A critical gap in the field of neuroAIDS research is the identification of reliable 
molecular markers linked with progression as well as distinct subtypes of HIV-
associated CNS disease.  Currently available clinical and laboratory markers of 
HIV/CNS disease may be less reliable in the HAART era.  The identification of 
molecular markers would be beneficial to track HIV/CNS disease progression in the 
era of HAART and also provide insights into mechanisms of neuropathogenesis.  Such 
markers may also lead to defining common pathways in the pathophysiology of HAD and 
other neurodegenerative diseases such as Parkinson’s disease, Huntington’s disease, 
Alzheimer’s disease, amyotrophic lateral sclerosis, and multiple sclerosis.

The goal of this RFA is to stimulate research to identify and characterize novel 
molecular and genetic markers associated with HIV-associated nervous system 
disease.  Research on the role of unique molecular and genetic markers in defining 
mechanisms of neuropathogenesis, host genetic susceptibility to development of CNS 
disease, and response to treatment are also relevant to this initiative.

Studies to be funded in response to this RFA could include, but are not limited to:

o  Microarray analysis of HIV-infected human CNS tissue or animal models of 
neuroAIDS at various stages of disease progression to identify modulation of unique 
genes.  Genes of interest can be further characterized to delineate their molecular 
identity as well as their functional role in neuropathogenesis.

o  Use of proteomics to uncover protein signatures associated with HIV infection in 
various peripheral and CNS cell populations and biological fluids of patients at 
various stages of disease progression.  Protein chip technologies may be utilized 
to identify unique protein profiles associated with neurological and 
neuropsychiatric manifestations of HIV infection.

o  Use of neuroimaging approaches such as proton magnetic resonance spectroscopy (1H 
MRS) and functional MRI (fMRI) to delineate key biological markers that correlate 
with disease symptoms and progression.  Neuroimaging studies are also useful to 
establish relationships between spectroscopic markers and histopathologic markers 
of neuronal health and inflammation. Studies of the role of unique inflammation-
related markers identified by neuroimaging, in the pathophysiology of neuroAIDS, 
are relevant.

o  Role of novel markers of immune activation and tissue damage (chemokines, 
cytokines, and other inflammatory mediators) as prognostic indicators of HIV-
induced nervous system disease progression and response to therapy.  Mechanistic 
studies of novel immune activation markers and their contribution to 
neuropathogenesis are of particular interest.

o  Studies of markers on microglial cells, endothelial cells, astrocytes, and 
neurons, reflecting HIV-induced cellular dysfunction or apoptosis, that not only 
serve as useful indicators of disease progression but also provide insights into 
mechanisms of development of nervous system disease.

o  Identification of novel markers of oxidative stress resulting from HIV infection 
of brain and interrelationship with neuronal injury as well as response to therapy.
 
o  Studies of molecular markers and signatures linked with HIV-associated 
opportunistic infections and co-infections in domestic and international settings.

o  Studies of actions of abused drugs on neurologic disease states using the 
techniques and approaches described herein to understand drug actions.  Also, 
studies of endogenous drug systems (e.g., opioid or cannabinoid systems) in the 
manifestations of HIV and related diseases are appropriate.

o  Studies of host genetic factors and markers that are associated with 
susceptibility and progression of HIV-associated nervous system disease.

o  Pharmacogenomic studies to identify genetic markers and polymorphisms linked 
with host response to anti-retroviral therapy.  For example, polymorphisms in the 
mdr gene are associated with differences in protease inhibitor levels and magnitude 
of CD4+ count recovery under therapy. 

MECHANISM OF SUPPORT

This RFA will use NIH research project grant (R01) and exploratory developmental 
grant (R21) award mechanisms.  As an applicant you will be solely responsible for 
planning, directing, and executing the proposed project.  The R21 mechanism (see 
http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html) is intended to 
encourage new exploratory/developmental research projects by providing support for 
the early stages of their development.  For example, such projects could assess the 
feasibility of a novel area of investigation or a new experimental system that has 
the potential to enhance health-related research.  These studies may involve 
considerable risk but may lead to a breakthrough in a particular area, or to the 
development of novel techniques, agents, methodologies, models or applications that 
could have a major impact on a field of biomedical, behavioral, or clinical 
research.

Applications for R21 awards should describe projects distinct from those supported 
through the traditional R01 mechanism.  For example, long-term projects, or 
projects designed to increase knowledge in a well-established area will not be 
considered for R21 awards.  Applications submitted under this mechanism should be 
exploratory and novel.  These studies should break new ground or extend previous 
discoveries toward new directions or applications.

R21 applications may request a project period of up to two years with a combined 
budget for direct costs of up $275,000 for the two-year period.  For example, you 
may request $100,000 in the first year and $175,000 in the second year.  The 
request should be tailored to the needs of your project. Normally, no more than 
$200,000 may be requested in any single year.   

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 December 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

The NIMH intends to commit approximately $1 million and NIDA intends to commit 
$500,000 in FY 2005 to fund 3 to 5 new and/or competitive continuation grants in 
response to this RFA.  An applicant may request a project period of up to 5 years 
for R01 and 2 years for R21.  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 the IC(s) 
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

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:

Jeymohan Joseph, Ph.D.
Chief, HIV Neurovirology, Genetics and Molecular Therapeutics Program
Center for Mental Health Research on AIDS
National Institute of Mental Health
6001 Executive Boulevard, Room 6202
Bethesda, MD  20892
Telephone:  (301) 443-3012
FAX:  (301) 443-9719
Email:  jjeymoha@mail.nih.gov

Charles Sharp, Ph.D.
Division of Neuroscience and Behavioral Research
National Institute on Drug Abuse
6001 Executive Boulevard, Room 4282, MSC 9555
Bethesda, MD  20892-9555 
Telephone:  (301) 443-1887
FAX:  (301) 594-6034
Email:  cs107m@nih.gov

o  Direct your questions about peer review issues to:

Michael Kozak, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6138, MSC 9609
Bethesda, MD  20892-9608
Telephone:  (301) 443-1340
FAX:  (301) 443-4720
Email:  kozakm@mail.nih.gov

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

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

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse
6101 Executive Boulevard, Suite 270, MSC 8403
Bethesda, MD  20892-8403
Telephone:  (301) 443-6710
FAX:  (301) 594-6849
Email:  gf6s@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 IC 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:

Jeymohan Joseph, Ph.D.
Chief, HIV Neurovirology, Genetics and Molecular Therapeutics Program
Center for Mental Health Research on AIDS
National Institute of Mental Health
6001 Executive Boulevard, Room 6202
Bethesda, MD  20892
Telephone: (301) 443-3012
FAX: (301) 443-9719
Email: jjeymoha@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/labels.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
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:

Jean Noronha, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6154, MSC 9609
Bethesda, MD  20892-9663
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 443-3367
FAX:  (301) 443-4720
Email:  jnoronha@mail.nih.gov

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 assignment 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 
unfunded application, originally submitted as an investigator-initiated 
application, is to be submitted in response to an RFA, it is to be prepared as a 
NEW application.  That is, the application for the RFA must not include an 
Introduction describing the changes and improvements made, and the text must not be 
marked to indicate the changes from the previous unfunded version of the 
application.

PEER REVIEW PROCESS

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the participating ICs.  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 the 
NIMH and 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 Councils of the 
participating ICs.

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.

SIGNIFICANCE:  Does this study address an important problem? If the aims of the 
application are achieved, how will scientific knowledge be advanced?  What will be 
the effect of these studies on the concepts or methods that drive this field?

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

INNOVATION:  Does the project employ novel concepts, approaches or methods? Are the 
aims original and innovative? Does the project challenge existing paradigms or 
develop new methodologies or technologies?

INVESTIGATOR:  Is the investigator appropriately trained and well suited to carry 
out this work?  Is the work proposed appropriate to the experience level of the 
principal investigator and other researchers (if any)?

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

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

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK:  The involvement of human subjects 
and protections from research risk relating to their participation in the proposed 
research will be assessed. (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).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH:  If vertebrate animals are to be 
used in the project, the five items described under Section f of the PHS 398 
research grant application instructions (rev. 5/2001) will be assessed.

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:    April 12, 2004
Application Receipt Date:         May 11, 2004
Peer Review Date:                 June 2004
Council Review:                   September 2004
Earliest Anticipated Start Date:  December 1, 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 AND SAFETY MONITORING PLAN:  Data and safety monitoring is required for all 
types of clinical trials, including physiologic, toxicity, and dose-finding studies 
(phase I); efficacy studies (phase II); efficacy, effectiveness and comparative 
trials (phase III).  The establishment of data and safety monitoring boards (DSMBs) 
is required for multi-site clinical trials involving interventions that entail 
potential risk to the participants.   (NIH Policy for Data and Safety Monitoring, 
NIH Guide for Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

SHARING RESEARCH DATA:  Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking $500,000 or more in direct 
costs in any single year are expected to include a plan for data sharing or state 
why this is not possible. http://grants.nih.gov/grants/policy/data_sharing  
Investigators should seek guidance from their institutions, on issues related to 
institutional policies, local IRB rules, as well as local, state and Federal laws 
and regulations, including the Privacy Rule. Reviewers will consider the data 
sharing plan but will not factor the plan into the determination of the scientific 
merit or the priority score.

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

All investigators proposing clinical research should read the "NIH Guidelines for 
Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, 
October, 2001," published in the NIH Guide for Grants and Contracts on October 9, 
2001 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a 
complete copy of the updated Guidelines 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.

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.healthypeople.gov/.

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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