IMMUNE SYSTEM DEVELOPMENT AND THE GENESIS OF ASTHMA

RELEASE DATE:  July 25, 2003

RFA: AI-03-041

National Institute of Allergy and Infectious Diseases (NIAID)
 (http://www.niaid.nih.gov)
National Heart, Lung, and Blood Institute (NHLBI)
 (http://www.nhlbi.nih.gov)

CATALOGUE OF FEDERAL DOMESTIC ASSISTANCE NUMBERS:
No. 93.855, Immunology, Allergy, and Transplantation Research
No. 93.856, Microbiology and Infectious Diseases Research
No. 93.838, Lung Diseases Research

LETTER OF INTENT RECEIPT DATE: October 21, 2003

APPLICATION RECEIPT DATE: November 21, 2003

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism 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

A considerable body of evidence suggests that abnormal function of the immune 
system is central to the pathogenesis of asthma, and recent studies indicate 
that the events that set the stage for the development of the asthma phenotype 
may occur during gestation and infancy.  The purpose of this RFA is to 
stimulate research on immune function in early life in order to define the 
cellular and molecular mechanisms underlying the development of asthma and to 
use this new information to devise strategies for the effective prevention or 
reversal of the disease without compromising the integrity of the immune 
system.  Although some aspects of the developing immune system are well 
understood, much remains to be learned about functional capabilities and 
molecular regulation at the early stages of immune development.  With new 
technologies, it is now feasible to conduct definitive studies in this area of 
research.  Identification of the cellular and molecular processes involved in 
the onset of asthma will provide the basis for developing immune-based 
treatment and prevention strategies that are not hampered by the limitations 
of current therapies. 

RESEARCH OBJECTIVES

Approximately 20 million Americans have physician-diagnosed asthma, and more 
than 12 million have had an asthma attack within the past year.  Asthma 
results in more than 130 million days of restricted activity, approximately 
500,000 hospitalizations, and nearly 5000 deaths each year in the U.S. The 
morbidity and mortality associated with asthma are disproportionately high 
among children, particularly those who reside in the inner city. African 
Americans are hospitalized for asthma three times more often than other 
Americans, and African Americans and Hispanic Americans living in inner cities 
are two to six times more likely to die from asthma.  Although the mortality 
associated with asthma is relatively low, the economic burden is high, with an 
estimated cost for asthma in the U.S. of $12.7 billion in 1998.  In spite of 
recent advances in understanding the mechanisms underlying asthma and 
improvements in medications used to treat the disease, the adverse impact on 
public health continues to grow.  For example, the prevalence of asthma has 
increased by more than 80% in all age and ethnic groups over the past two 
decades.  
   
The management of asthma is complex, and adequate control is difficult to 
maintain because patients are required to comply with daily, multi-drug 
regimens.  Severe asthma poses a greater problem, even with an optimal 
management plan. In addition, many of the drugs currently used to treat asthma 
have a number of undesirable side effects, and, in some cases, overuse can 
actually lead to worsening of the disease. Research during the past two 
decades has significantly improved our appreciation of the role of airway 
inflammation and immune dysfunction in the pathogenesis of asthma and has led 
to the identification of the cells and molecules involved, but this knowledge 
has yet to be translated into the clinical arena.  Consequently, it is 
important to consider new approaches to dealing with the growing asthma 
epidemic. Results of recent studies suggesting that the origins of asthma 
occur early in life coupled with new technologies that have the potential to 
elucidate the bases of complex biological problems provide the opportunity to 
focus on the cellular and molecular immune mechanisms that lead to the onset 
of asthma and disease progression.  Research in this important area should 
yield vital new information required to devise novel immune-based therapies as 
well as rational strategies for disease prevention.
 
Epidemiological studies have identified a number of environmental risk factors 
associated with the development of asthma (or pathophysiological precursors of 
asthma such as repeated wheeze), including viral infections and exposure to 
cockroach allergen or tobacco smoke.  It is thought that during infancy and, 
perhaps, during gestation these environmental factors affect immune system 
development and prime genetically susceptible individuals for the later 
expression of asthma, usually by age five or six.  The mechanisms leading to 
priming are poorly understood but may involve the persistence after birth of 
the Th2 phenotype, which is characteristic of the intrauterine environment.  
It is of interest that other factors, such as endotoxin, farm animals or furry 
pets, appear to protect against the development of asthma, perhaps by 
stimulating regulatory T cells and/or establishing a favorable Th1/Th2 
balance.  Collectively, these findings suggest that early life changes in 
immune function induced by environmental factors determine whether an 
individual is likely to develop asthma or is protected against the disease.
 
If this hypothesis is correct, it should be possible to devise strategies that 
block the onset of asthma or slow the progression of the disease by targeting 
specific immune processes involved in establishing the asthma phenotype. This 
will require a better understanding of the cellular and molecular mechanisms 
involved in early life changes in immune function that contribute to the 
development of asthma.  Certain aspects of the developing immune system have 
been well characterized, including the ontogeny of B and T cell repertoires, 
but little is known about the regulation of immune function during the early 
stages of development, particularly with respect to priming for the expression 
of asthma. This includes the temporal characteristics of priming, whether the 
process is reversible, the applicability of the Th1/Th2 paradigm to humans, 
the cellular and molecular basis of the protection provided by certain 
environmental factors and interactions between the innate and adaptive 
elements of the developing immune system.

Innovative research in these important areas is essential to further elucidate 
the cellular and molecular mechanisms involved in the development and 
progression of asthma.  This will require a variety of approaches, including 
birth cohort studies incorporating informative mechanistic investigations. 
Recent advances in technology ranging from genomic and proteomic tools to 
high-resolution imaging and non-invasive methods for measuring lung function 
in infants should facilitate such studies.  Depending on study design, 
outcomes could include the development of asthma or early life surrogate 
markers that are strongly associated with the later development of asthma, 
such as frequent wheezing.  Although the emphasis of this RFA is research in 
humans, projects involving animal models will be considered responsive if they 
are justified on the basis of technical feasibility and relevance to human 
asthma.  Hypothesis driven, mechanistic studies on how the developing immune 
system affects susceptibility to, or protects against, asthma development are 
the focus of this RFA.  Long-term epidemiological studies without accompanying 
mechanistic studies are not appropriate for this RFA.

Examples of research areas to be supported under this RFA include, but are not 
limited to:  early cellular and molecular markers of asthma onset and 
progression; factors that regulate the processing and presentation of 
aeroallergens in the infant lung and the effect of early exposures on the 
developing lung; the effect of timing, dose and route of antigen exposure on 
determination of susceptibility to asthma; mechanisms involved in the 
initiation and amplification of aeroallergen-specific IgE synthesis; 
regulation of primary B and T cell responses; role of the innate immune system 
and tolerance in determining susceptibility to asthma; immune-mediated 
mechanisms of protection against the development of asthma; effects of 
maternal and environmental asthma risk factors on immune function early in 
life; and translational research focused on new immune-based therapies and 
asthma prevention strategies, including proof of concept studies in humans.  

MECHANISM OF SUPPORT

This RFA will use the NIH individual research project grant (R01) award. The 
total requested project period for an application submitted in response to 
this RFA may not exceed five years for an R01. The applicant 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 July 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 for NEW applications described in the instructions to the PHS 398 
application.

This RFA uses just-in-time concepts. It also uses the modular as well as the 
non-modular budgeting formats (see 
https://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if an 
investigator is submitting an application with direct costs in each year of 
$250,000 or less, use the modular format. Otherwise follow the instructions 
for non-modular research grant applications. This program does not require 
cost sharing as defined in the current NIH Grants Policy Statement at 
https://grants.nih.gov/archive/grants/policy/nihgps_2001/part_i_1.htm.

FUNDS AVAILABLE

The participating ICs intend to commit approximately $ 5.6 million in FY 2004 
to fund 8 to 12 new and/or competitive continuation grants in response to this 
RFA.  An applicant may request a project period of up to five years.  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 
vary. Although the financial plans of the ICs 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

The applicant may submit (an) application(s) if the 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
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

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. AN 
UPDATED NIAID policy was published in the NIH Guide on July 8, 2002 and is 
available at:
https://grants.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html.
The full policy, including terms and conditions of award, is available 
at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf.

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 questions about scientific/research issues to:

Ken Adams, Ph.D.
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases
Room 3103, MSC-6601
6610 Rockledge Drive
Bethesda, MD 20892-6601
Telephone: (301) 496-8973
FAX: (301) 402-8179
Email: ka93x@nih.gov 

Patricia Noel, Ph.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
Room 10222, MSC-7952
6701 Rockledge Drive, MSC-7952
Bethesda, MD  20892-7952
Telephone:  (301) 435-0202
FAX:  (301) 480-3557
Email:  pn61t@nih.gov 

o Direct questions about peer review issues to:

Edward W. Schroder, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3136 MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) 435-8537
FAX: (301) 402-2638
Email: es170m@nih.gov

o Direct questions about financial or grants management matters to:

Ann Devine  
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2118, MSC-7614
6700-B Rockledge Drive
Bethesda, MD 20892-7614
Telephone: (301) 402-5601
Email: ad22x@nih.gov

Ephraim A. Johnson
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Suite 7044, MSC-7926
6701 Rockledge Drive
Bethesda, MD  20892-7926
Telephone:  (301) 594-9529
FAX:  (301) 480-3310
Email:   ej47e@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:

Edward W. Schroder, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3136, MSC-7616
6700-B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) 435-8537
FAX: (301) 402-2638
Email: es170m@nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001). The PHS 398 is available at 
https://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format. For further assistance contact GrantsInfo, Telephone (301) 710-0267, 
Email: GrantsInfo@nih.gov.

SUPPLEMENTAL INSTRUCTIONS

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 
https://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 
https://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: 
https://grants.nih.gov/grants/funding/phs398/label-bk.pdf.

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the Checklist, and three signed, photocopies, in 
one package to:

Center For Scientific Review
National Institutes Of Health
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 exact copies of the grant 
application and all five sets of any appendix material must be sent to:

Edward W. Schroder, Ph.D.
Review Processing Unit, Room 3136
Scientific Review Program, DEA/NIAID/NIH/DHHS
6700-B Rockledge Drive, MSC-7616
Bethesda, MD 20892-7616
Bethesda, MD 20817 (for express/courier service)

APPLICATION PROCESSING: Applications must be received by 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.

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. While the 
investigator may still benefit from the previous review, the RFA application 
is not to state explicitly how.

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.

PEER REVIEW PROCESS

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

Applications that are complete and responsive to the RFA will be evaluated for 
scientific and technical merit by an appropriate peer review group convened by 
NIAID in accordance with the review criteria stated below. As part of the 
initial merit review, all applications will:

o Receive a written critique
o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o Receive a second level review by the National Advisory Allergy and 
Infectious Diseases Council and/or the National Heart, Lung, and Blood 
Advisory Council

REVIEW CRITERIA

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

o Significance
o Approach
o Innovation
o Investigator
o Environment

The scientific review group will address and consider each of these criteria 
in assigning the application's overall score, weighting them as appropriate 
for each application. 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 CONSIDERATIONS

DATA SHARING: The adequacy of the proposed plan to share data.

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:   October 21, 2003
Application Receipt Date:        November 21, 2003
Peer Review Date:                March 2004
Council Review:                  May 2004
Earliest Anticipated Start Date: July 2004

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit of the proposed project 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

MONITORING PLAN AND DATA AND SAFETY MONITORING BOARD: Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures. In addition, it is NIH policy that 
all clinical trials require data and safety monitoring, with the method and 
degree of monitoring being commensurate with the risks (NIH Policy for Data 
Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: 
https://grants.nih.gov/grants/guide/notice-files/not98-084.html).

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

All investigators proposing clinical research should read the AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001
(https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines are available at 
https://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 
https://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. 
This policy announcement is in the NIH Guide for Grants and Contracts 
Announcement, dated June 5, 2000, at 
https://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 
https://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 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 
https://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 
https://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 PA 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 Catalogue of Federal Domestic Assistance at 
http://www.cfda.gov/ in the following citations: No. 93.855, Immunology, 
Allergy, and Transplantation Research, No. 93.856, Microbiology and Infectious 
Diseases Research, and No. 93.838, Lung 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 
https://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. All awards are 
subject to the terms and conditions, cost principles, and other considerations 
described in the NIH Grants Policy Statement.

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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