INTER-RELATIONSHIPS OF SLEEP, FATIGUE, AND HIV/AIDS
 
RELEASE DATE:  October 27, 2003
 
RFA Number:  RFA-HL-04-010

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATIONS: 
National Heart, Lung, and Blood Institute (NHLBI)
 (http://www.nhlbi.nih.gov)
National Institute of Mental Health (NIMH)
 (http://www.nimh.nih.gov/)    

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.233, 93.853, 
93.837, 93.838, 93.839
 
LETTER OF INTENT RECEIPT DATE: February 13, 2004
APPLICATION RECEIPT DATE: March 15, 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 Special Requirements
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 primary goal of this initiative is to elucidate the etiology of 
sleep disturbances and fatigue associated with human immunodeficiency 
virus (HIV) infection and acquired immunodeficiency disease syndrome 
(AIDS).  An improved understanding of this etiology will help in the 
development of approaches to improve the sleep and quality of life of  
HIV-infected patients and improve our fundamental understanding of the 
relationship between sleep and chronic infections in particular and 
chronic diseases in general.

RESEARCH OBJECTIVES

Between 850,000 and 950,000 Americans are living with HIV infection and 
suffering from devastating effects on health, performance, and overall 
quality of life (QOL). As new therapies extend life expectancy of HIV 
patients, long term adverse impacts on QOL become increasingly 
important. Although relatively unstudied, sleep disturbance and fatigue 
are highly prevalent and disabling symptoms in a majority of 
individuals infected with human immunodeficiency virus (HIV).  Sleep 
complaints are among the first symptoms of HIV infection and correlate 
with decreasing CD4+ lymphocyte counts in otherwise asymptomatic HIV 
seropositive individuals.   Fatigue symptoms are associated with 
increased napping, diminished alertness, difficulty falling asleep, and 
frequent awakening during sleep.  Polysomnographic studies indicate 
that HIV infection disrupts the normal cycle of alternating rapid eye 
movement (REM) and non-REM periods associated with restorative sleep; 
advanced HIV infection is associated with a loss of normal sleep 
patterns.  These impairments in sleep quality may diminish 
immunological and cognitive-motor function. The onset of these 
disturbances in sleep architecture occurs early in the course of HIV 
disease and appears to be a characteristic of the long clinical latency 
preceding the development of acquired immunodeficiency disease syndrome 
(AIDS).   For patients with HIV infection, sleep disturbance and 
fatigue interfere with daily activities, diminish the quality of life, 
and contribute to a greater risk of unemployment.  Advanced HIV 
infection is associated with a loss of normal sleep patterns.  

Common complications of advanced HIV infection, such as peripheral 
neuropathy, can also be a source of sleep disturbance and exacerbate 
fatigue symptoms.  Some findings suggest that symptoms of sleep 
disturbance and fatigue are independently associated with survival 
among people with HIV infection.  Although relatively little is known 
about the pathophysiology or etiology of sleep disturbances and fatigue 
in patients with HIV disease, it is known that there are reciprocal 
interactions between sleep and neuroendocrine and immune factors. For 
example, immune molecules alter sleep architecture, sleep deprivation 
alters neuroendocrine and immune responses, immune system activation 
and neuroendocrine responses alter sleep, and sleep quality appears to 
affect the course of and susceptibility to infectious diseases in 
general.

Clarification of the relationships among sleep, fatigue, and HIV/AIDS 
may yield novel possibilities for new ways to study and manage this 
disease.  Studies are needed to elucidate mechanisms associated with 
both the presence of HIV infection and decrements in sleep and 
wakefulness.  Early immunological responses to peripheral HIV infection 
are known to alter the profile of circulating cytokines implicated in 
the regulation of physiological sleep.  These acute phase response 
cytokines are elevated in the blood of HIV-infected individuals, and 
produce fatigue when administered in human and animal models.  Studies 
are needed to determine whether blood brain barrier permeability to 
these cytokines is compromised after HIV infection, and to elucidate 
central mechanisms by which increased cytokine levels alter sleep, the 
biological clock, body temperature, and other regulators of sleep and 
wakefulness.  Recent findings from animal studies suggest that shedding 
of the HIV envelope-coat glycoprotein gp120 may mediate at least some 
sleep abnormalities.  Central mechanisms by which HIV gp120 leads to 
disturbance of sleep and wakefulness need to be elucidated.  Sleep 
disturbances also produce abnormalities in hypothalamic-pituitary-
adrenal (HPA) axis hormone secretions such as cortisol and growth 
hormone. It is not well understood, however, to what extent these 
sleep-related abnormalities contribute to the acute phase response of 
HIV infection, the progressive decline in humoral and cellular 
immunity, the decline of neuropsychological function in AIDS-related 
dementia, and the wasting syndrome associated with late-stage AIDS.  
The severity of sleep disturbance and potential developmental 
consequences of pediatric and especially infant HIV have also not been 
studied.  Research is needed to elucidate the relationship of 
peripheral neuropathy and other symptoms of advanced HIV infection to 
sleep disturbance and fatigue.  

HIV infection may also increase the risk of sleep disordered breathing.  
Adenotonsillar hypertrophy is an early manifestation of HIV infection 
and can lead to reductions in upper airway dimensions that increase the 
risk for sleep-disordered breathing in HIV-infected adults compared to 
the general population.  Accumulating evidence indicates that mild to 
moderate sleep-disordered breathing may be an independent risk factor 
for hypertension, cardiovascular disease, and stroke.  Whether HIV 
infection modifies these risks is unknown.  Studies are needed to 
determine the epidemiological risks, natural history, and causal 
mechanism(s) linking HIV-related infections, lymphadenopathy, and other 
complications of HIV infection to an increased risk of sleep-disordered 
breathing.  Screening instruments and optimal treatment regimens for 
airway obstruction also need to be developed since available surgical 
treatment approaches indicated in selected patients present significant 
added risks for HIV-infected adults.

Insomnia, independent of drug or alcohol use, appears to be a highly 
prevalent and under-diagnosed disorder in patients with HIV-infection.   
It is also a common side-effect of anti-retroviral therapies used in 
HIV treatment.  Epidemiological and clinical research are needed to 
elucidate the neurological and neurobehavioral characteristics of 
insomnia in HIV-infected individuals, the role in the progression of 
HIV infection, and the relationship to other symptoms of HIV infection 
including pain, anxiety, and depression.  Developing biomarkers and 
imaging techniques that define brain sites associated with insomnia may 
lead to indicators alerting to potential HIV infection.

There are a number of research directions that could be pursued to 
elucidate the etiology of sleep disturbances and fatigue associated 
with HIV infection and AIDS.  Clinical and animal model based research 
using mechanistic neurophysiological, neuroanatomical, and 
pharmacological approaches are encouraged.  Examples of studies that 
would be responsive to this program include but are not restricted to 
the following:  

o Elucidate mechanisms underlying sleep abnormalities and circadian 
dysrhythmia in human HIV/AIDS, or in animal models infected with 
viruses comparable to HIV.

o Elucidate the cellular or neural basis for changes in the regulation 
of biological clock and homeostatic sleep mechanisms responsible for 
entrained and free running circadian rhythms as a function of infection 
with viruses comparable to HIV.

o Identify potential exacerbating effects of sleep and circadian 
disturbance on the severity of HIV infection and progression to AIDS, 
or in animal models infected with viruses comparable to HIV.
            
o Identify abnormalities in restorative functions of sleep contributing 
to symptoms of fatigue and excessive daytime sleepiness as a function 
of HIV infection and AIDS. 

o Elucidate mechanisms linking sleep and circadian disturbances in 
HIV/AIDS to cardiopulmonary, endocrine, immunological, and other 
pathophysiological sequalae of HIV infection and AIDS.

o Elucidate sleep abnormalities contributing to HIV-related 
neurocognitive dysfunction and excessive daytime sleepiness.

o Identify differences in sleep/alertness among HIV/AIDS patient groups 
that vary with respect to peripheral nerve pathology.

o Elucidate biological, cellular, and molecular mechanisms by which HIV 
or HIV viral proteins interact with the host to disturb normal sleeping 
patterns, and the interactions between the HIV proteins and primary and 
secondary targets in the central nervous system.

o Elucidate the effects of sleep disturbance and fatigue on HIV disease 
progression, as indicated by immunological and clinical indicators of 
disease progression, and identify biological mediators and biomarkers 
of such interactions.

MECHANISM OF SUPPORT
 
This RFA will use NIH R01 award mechanism.  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, 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 
budgetingas 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/archive/grants/policy/nihgps_2001/part_i_1.htm. 

FUNDS AVAILABLE 
 
The NHLBI intends to commit approximately $2,000,000 and NIMH 
approximately $500,000 in FY 2004 to fund four to five new and/or 
competitive continuation grants in response to this RFA. An applicant 
may request a project period of up to four years and a budget for 
direct costs of up to $350,000 per year.  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 Institutes 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 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.   
 
SPECIAL REQUIREMENTS
 
In order to be considered responsive to this announcement, applications 
must propose hypothesis-driven studies that focus on elucidating the 
etiology of sleep disturbances and fatigue associated with HIV 
infection and AIDS.  Studies of sleep disorders must be closely coupled 
to the goal of elucidating pathophysiology associated with HIV 
infection and AIDS in order to be considered responsive to this RFA.  
Applications focused on the transfer of established methods or 
overcoming technical barriers such as the measurement of sleep will not 
be accepted.  Applications centered on developing large cohorts for 
epidemiology or interventions for HIV/AIDS or sleep disorders would not 
be appropriate. 

Collaborations and consortia promoting interdisciplinary approaches 
between scientists studying the pathophysiology of HIV infection and 
AIDS and sleep or circadian researchers are strongly encouraged. In 
such cases, each participant's contribution should be identified and 
well-integrated into the overall experimental design.  Applications 
proposing to include data collection from normal human subjects or 
animal models must provide a strong rationale that is clearly relevant 
to the goal of elucidating the etiology of sleep disturbance and 
fatigue associated with HIV infection and AIDS.  

Upon initiation of the program, the sponsoring Institutes may organize 
periodic meetings to encourage the exchange of information among 
investigators who participate in this program. Travel funds for a two 
day meeting each year, most likely to be held in Bethesda, Maryland, 
must be included in the budget calculation. Applicants must include a 
statement indicating their willingness to participate in these 
meetings.  

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:

Michael J. Twery, Ph.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Bethesda, MD 20892-7952 
Telephone: (301) 435-0202 
FAX: (301) 480-3557 
Email: twery@nih.gov 

Kathy Kopnisky, Ph.D.
Center for Mental Health Research on AIDs
National Institute of Mental Health
6001 Executive Boulevard, Room 6199
Bethesda, MD  20892-9619
Telephone: (301) 443-7726
FAX: (301) 443-9719
Email: Kkopnisky@NIH.gov 

o Direct your questions about peer review issues to:

Anne Clark, Ph.D.
Chief, Review Branch
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7214, MSC 7924
Bethesda, MD 20892 (20817 for express/courier service)
Telephone: (301) 435-0270 
FAX: (301) 480-3541 
Email: clarka@nhlbi.nih.gov 

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

Robert Pike
Grants Operations Branch
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Bethesda, MD 20892-7926
Telephone: (301) 435-0171 
FAX: (301) 480-3310 
Email: piker@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 by mail or E-mail 
to Anne Clark at the above address.

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 five collated sets of appendix material must be sent to Anne Clark 
at the above address for peer review questions. 

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 NHLBI and NIMH.  Incomplete and/or 
nonresponsive applications will not be reviewed.
  
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 National Heart, Lung, and Blood Institute 
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 an appropriate national advisory 
council or board.
 
REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
In the written comments, reviewers will be asked to evaluate 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
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 

SHARING RESEARCH DATA: The reasonableness of the data sharing plan or 
the rationale for not sharing research data will be assessed by the
reviewers.  However, reviewers will not factor the proposed data 
sharing plan into the determination of scientific merit or priority 
score. 
http://grants.nih.gov/grants/policy/data_sharing/index.htm
 
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 13, 2004
Application Receipt Date:  March 15, 2004
Peer Review Date:  May-June, 2004
Council Review:  September, 2004
Earliest Anticipated Start Date:  September, 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).  

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.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.


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.