PA-04-080: PATHOGENESIS OF SARS LUNG DISEASE: IN VITRO STUDIES AND ANIMAL MODELS

PATHOGENESIS OF SARS LUNG DISEASE: IN VITRO STUDIES AND ANIMAL MODELS

RELEASE DATE: April 1, 2004

PA NUMBER: PA-04-080

Expiration Date for R01 Non-AIDS Applications: November 2, 2006
Expiration Date for R01 AIDS and AIDS-Related Applications: January 3, 2007

January 3, 2007 - Effective with the February 5, 2007 submission date,
all R01 applications must be submitted through Grants.gov using
the electronic SF424 (R&R) application. Accordingly, this funding
opportunity expires on January 3, 2007. Unsolicited or
investigator-initiated R01 electronic SF424 (R&R) applications may
be submitted through the Research Project Grant (Parent R01) announcement.

Department of Health and Human Services (DHHS)

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

COMPONENT OF PARTICIPATING ORGANIZATION:
National Heart, Lung, and Blood Institute (NHLBI)
(http://www.nhlbi.nih.gov/index.htm)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.838

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
o Research Objectives
o Mechanism(s) of Support
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Supplementary Instructions
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS PA

The goal of this program announcement is to invite research applications to
rapidly advance understanding of the pathogenesis of severe acute respiratory
syndrome (SARS) in the lung using the following:

o in vitro techniques (especially, using human viral isolates, human tissues
and cells, and other biological samples)
o existing animal models of related coronavirus infections (e.g., porcine
respiratory CoV)
o non-human primate models of SARS
o new ferret models of SARS
o new rodent models of SARS
o other appropriate animal models of SARS

The PA invites R01 applications for both high risk hypothesis generating
research and hypothesis driven projects (if sufficient preliminary data are
available), relevant to the pathogenesis of human lung disease caused by the
human SARS coronavirus (SARS-CoV).

RESEARCH OBJECTIVES

SARS, manifested by fever, pulmonary infiltrates, and often respiratory failure and
death, infected more than 8000 people worldwide during the winter and spring of 2003.
Overall, the death rate for SARS is estimated at 9.6%, but this rate is 50% or more
for patients over 60 years of age. The World Health Organization (WHO) and the
Centers for Disease Control (CDC) quickly identified a new human coronavirus, SARS-
CoV, which appears to have “jumped” species from an animal reservoir, to infect humans
and cause SARS. At present, the outbreak has subsided, due to rigorous public health
measures and probably to the seasonal nature of the coronavirus life cycle. Questions
about viral persistence in asymptomatic animal or human hosts or how SARS might emerge
next remain unanswered for now. The mechanism is not known. It has been postulated
that this might occur as a result of persistence and shedding of virus by asymptomatic
human hosts or as a consequence of human contact with animals that are harboring the
virus (possibly civet cats in China). A few new cases have been reported from China
in December 2003 and January 2004, but fortunately the disease does not appear to have
spread. At least some cases appear to have had contact with civet cats.

Clinical and histopathological descriptions from Hong Kong, Toronto, Taiwan and
elsewhere indicate that SARS causes severe pneumonia in a large proportion of infected
individuals. Many patients (19% of 196 studied in Toronto) develop an acute
respiratory distress syndrome (ARDS), usually during the second week of illness. The
pulmonary histopathology of severe cases of SARS appears typical of ARDS. Timing of
the lung damage suggests that much of the injury may be mediated by the host immune
system. However, the extent to which lung injury results from SARS-CoV itself, by
infection and replication in lung epithelial cells (and perhaps other cells), and the
extent to which it is caused by the host immune responses to the virus are unclear.
Co-existing infections (e.g., human paramyxovirus) are present in some specimens and
may possibly play a role in triggering events leading to severe lung damage.
Treatment with the wide spectrum antiviral drug ribavirin does not seem to be of any
benefit. Since it appears that the pathogenesis of lung disease in SARS may be
largely due to an immune component, corticosteroids have been administered in an
attempt to control this. The use of corticosteroids to reduce lung injury is currently
controversial. Other immune modulating agents (interferons) are being screened and
considered for possible treatment studies, if there is a new outbreak of disease. An
issue for patients who survive SARS is the extent of residual lung damage and other
sequellae. Evidence of fibrosis, reported on lung biopsies and findings compatible
with fibrosis on follow-up high resolution CT scans support the need to study this.

At this time, very little is known about the pathogenesis of SARS in the lung.
Macaques have been infected in preliminary experiments and are reported to have lung
lesions similar to those seen in humans. Attempts to establish rodent models of lung
disease have not succeeded yet, but infection can be established in rodents and models
of other animal coronavirus diseases make it likely that a model may be established
soon, either by direct infection or by modifying the SARS-CoV genome. Recently,
ferrets and domestic cats have been infected with SARS-CoV. These animals can spread
infection. The ferrets become ill and die, not apparently from pneumonia, but the
model is reproducible.

Meanwhile, much essential information about the pathogenesis of SARS in the lung could
be gained from using established animal models of other coronaviruses and in vitro
studies of SARS-CoV interactions with lung and immune cells.

In addition to learning about how the virus infects lung cells, this PA specifically
encourages in vitro research on the role of lung collectins and other extracellular
lung host factors. It encourages studies of endothelial and epithelial permeability,
effects of SARS on fluid movements, and growth and differentiation of human lung cells
(alveolar epithelial cells, fibroblasts, etc.). Research on SARS-CoV interactions
with human lung and immune cells and tissues is the primary focus, but research using
engineered and related coronaviruses and animal cells pertinent to pathogenesis of
SARS may also be responsive.

This PA encourages pulmonary investigators to form collaborations to take full
advantage of already established animal models of coronavirus infection and newly
developed animal resources. Of equal importance, pulmonary investigators are
encouraged to use existing genetically altered mouse resources (e.g., the NHLBI
Programs of Genomic Applications (PGA)) and if necessary to develop novel mice,
engineered to incorporate or ablate components of immune function, to study the
pathogenesis of SARS lung injury. Collaborations with virologists to develop and
study chimeric viruses are encouraged. Chimeras might make it possible to use many
existing mouse models and reagents that could quickly provide data on mechanisms of
lung damage in SARS.

Great care will be needed to protect personnel and prevent spread of viruses to other
animals. Investigators will need to document that they have access to appropriate BSL3
level facilities and that the investigators and other personnel are appropriately
trained.

Research utilizing patient viral isolates, cells, tissue and other biological samples
is encouraged if these are available.

It may also be possible to gain useful information by working with adapted strains of
virus, e.g., a murine adapted strain or with existing animal models of related
coronavirus diseases (pig, mouse, cat, etc.,) that may not require such stringent
isolation.

Examples of the type of research topics and approaches that would be solicited under
this program announcement include (but are not limited to) the following:

Determine which lung structural cells (e.g., epithelial, endothelial, etc.,)and immune
and inflammatory cells support human SARS-CoV infection.

Study viral binding, receptors, co-receptors, replication, persistence, effects on
host cell gene expression, and apoptosis.

Investigate immunological aspects of SARS-CoV infection, e.g., elaboration of
cytokines, antigen presentation and effects of co-stimulation with other pathogens.

Address the role of immune responses, age related issues, surfactant proteins, and the
effects of co-morbidities (e.g., underlying emphysema, diabetes) using animal models
of SARS.

Elucidate pathogenesis by using animal models to study the effects of vaccines,
antiviral drugs, and immune modulating agents that might moderate the manifestations
of SARS in the lung.

MECHANISM(S) OF SUPPORT

This PA will use the NIH R01 award mechanism. As an applicant, you will be solely
responsible for planning, directing, and executing the proposed project.

This PA 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.

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
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

Investigators working with SARS-CoV and other potentially dangerous infectious agents
will need to document that they have access to carefully controlled BSL3 laboratories,
properly isolated animal housing, and the availability of appropriately trained
personnel. This program announcement requires that investigators who plan to work with
SARS-CoV and other agents needing BSL3 facilities must demonstrate close coordination
with groups that have BSL3 facilities and expertise.

This is not intended as a vaccine or drug development program. Studies in which
vaccines or drugs are used to elucidate the pathogenesis of SARS in the lung may be
considered responsive to this PA. However, studies that focus on vaccine and drug
development will not be considered responsive.

Work on normal lung tissue and cells may be used for comparison purposes, but to be
responsive to the PA the proposed research projects must focus on the pathogenesis of
SARS in the lung.

All applications submitted in response to this PA must include plans for sharing data
and other resources.

Grantee's Meetings

Upon initiation of the program, the NHLBI will sponsor meetings to encourage exchange
of information among investigators who participate in this program announcement. In
their budgets, applicants should include funds for annual one-day grantees' meetings,
most likely in Bethesda, Maryland. Applicants should also include a statement in
their applications indicating their willingness to participate in these meetings. The
first such meeting probably will take place about 12 months after the awards are
issued.

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA and welcome the opportunity to answer
questions from potential applicants. Inquiries may fall into two areas:
scientific/research and financial or grants management issues:

o Direct your questions about scientific/research issues to:

Hannah H. Peavy, M.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Suite 10018
Bethesda, MD 20892-7952
Phone: (301) 435-0222
Fax: (301) 480-3557
Email: peavyh@nhlbi.nih.gov

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

Robert Pike
Grants Management Officer
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7144, MSC 7926
Bethesda, MD 20892-7926
Telephone: (301) 435-0171
FAX: (301) 480-3310
Email: piker@nhlbi.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 is
available at http://grants.nih.gov/grants/funding/phs398/phs398.html n
an interactive format. For further assistance contact GrantsInfo,
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

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

APPLICATION RECEIPT DATES: Applications submitted in response to this program
announcement will be accepted at the standard application deadlines, which are
available at http://grants.nih.gov/grants/dates.htm. Application
deadlines are also indicated in the PHS 398 application kit.

SPECIFIC INSTRUCTIONS FOR MODULAR BUDGET GRANT APPLICATIONS: Applications requesting
up to $250,000 per year in direct costs must be submitted in a modular budget grant
format. The modular budget 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.

SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR:
Applications requesting $500,000 or more in direct costs for any year must include a
cover letter identifying the NIH staff member within one of NIH institutes or centers
who has agreed to accept assignment of the application.

Applicants requesting more than $500,000 must carry out the following steps:

1) Contact the IC program staff at least 6 weeks before submitting the application,
i.e., as you are developing plans for the study;

2) Obtain agreement from the IC staff that the IC will accept your application for
consideration for award; and,

3) Identify, in a cover letter sent with the application, the staff member and IC who
agreed to accept assignment of the application.

This policy applies to all investigator-initiated new (type 1), competing continuation
(type 2), competing supplement, or any amended or revised version of these grant
application types. Additional information on this policy is available in the NIH Guide
for Grants and Contracts, October 19, 2001 at:
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html.

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

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710
Bethesda, MD 20817 (for express/courier service)

APPLICATION PROCESSING: Applications must be mailed on or before the receipt dates
described at
http://grants.nih.gov/grants/funding/submissionschedule.htm. The CSR will not accept
any application in response to this PA that is essentially the same as one currently
pending initial review unless the applicant withdraws the pending application. The
CSR will not accept any application that is essentially the same as one already
reviewed. This does not preclude the submission of a substantial revision of an
unfunded version of an application already reviewed, but such application must include
an Introduction addressing the previous critique.

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

Applications submitted for this PA will be assigned on the basis of established PHS
referral guidelines. Appropriate scientific review groups convened in accordance with
the standard NIH peer review procedures (http://www.csr.nih.gov/refrev.htm) will
evaluate applications for scientific and technical merit.

As part of the initial merit review, all applications will:

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 written critique
o Receive a second level review by the appropriate national advisory council or board.

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of biological
systems, improve the control of disease, and enhance health. In the written comments,
reviewers will be asked to evaluate 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).
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

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 will be assessed.
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

Applicants requesting more than $500,000 in direct costs in any year of the
proposed research are expected to include a data sharing plan in their
application. 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 )

BUDGET: The reasonableness of the proposed budget and the requested period of support
in relation to the proposed research.

AWARD CRITERIA

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

o Scientific merit of the proposed project as determined by peer review
o Availability of funds
o Relevance to program 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 (Type1) 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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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