PAS-04-079: UNDERSTANDING AND PREVENTING BRAIN TUMOR DISPERSAL

UNDERSTANDING AND PREVENTING BRAIN TUMOR DISPERSAL

RELEASE DATE: March 25, 2004

PA NUMBER: PAS-04-079

The R01 portion of this funding opportunity has been replaced by PAS-07-196,
which now uses the electronic SF424 (R&R) application for February 5, 2007
submission dates and beyond.

March 2, 2006 (NOT-OD-06-046) – Effective with the June 1, 2006 submission date,
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using
the electronic SF424 (R&R) application. Accordingly, the R21 portion of this funding opportunity
expires on the date indicated below. Other mechanisms relating to this announcement will continue to
be accepted using paper PHS 398 applications until the stated expiration date below, or transition
to electronic application submission. A replacement R21 (PAS-06-201) funding opportunity announcement
has been issued for the submission date of June 1, 2006 and submission dates thereafter.

EXPIRATION DATE: for R21 Applications: March 2, 2006
Expiration Date for R01 Non-AIDS Applications: November 2, 2006
Expiration Date for R01 AIDS and AIDS-Related Applications: January 3, 2007

Department of Health and Human Services (DHHS)

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

COMPONENTS OF PARTICIPATING ORGANIZATION:
National Institute of Neurological Disorders and Stroke (NINDS)
(http://www.ninds.nih.gov)
National Cancer Institute (NCI)
(http://www.nci.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.853 (NINDS), 93.393 (NCI)

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
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 Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS PA

Many brain tumors are highly invasive and therefore extremely difficult to
treat. Cells from the primary tumor often infiltrate into surrounding brain
tissues, so that removal of the main tumor mass is not sufficient to prevent
recurrence. The goal of this Program Announcement with set-aside funds (PAS)
is to promote studies that: (1) identify the properties of brain tumor cells
that cause them to migrate; (2) determine how interaction of tumor cells with
normal brain elements affects migration; and (3) translate understanding of
these parameters into interventions that target invading tumor cells.
Interdisciplinary studies that apply new concepts and methodologies from
developmental neuroscience, genomics, precursor cell biology and other
related fields are particularly encouraged.

RESEARCH OBJECTIVES

Background

In November 2000, NINDS and NCI conducted a joint, comprehensive planning
effort called the Brain Tumor Progress Review Group (BT-PRG). The goal of
the BT-PRG was to identify the highest priorities in brain tumor research
(for a complete description of the results of the BT-PRG, see
http://prg.nci.nih.gov/brain/finalreport.html). One of the key scientific
goals established through this planning process was to increase our
understanding of brain tumor dispersal and translate this understanding into
more effective therapies for this devastating group of diseases.

Malignant brain tumors consist of a core mass and surrounding individual
cells that infiltrate into adjacent brain tissue. In recent years,
technologies for imaging and surgically removing brain tumors have improved.
However, neurosurgeons continue to observe that radical resection of primary
gliomas, the most common type of brain tumor, is often followed by growth of
secondary tumors that are not treatable by radiation or chemotherapy. This
observation suggests that invading cells are able to activate a molecular and
cellular program that makes them impervious to conventional therapies.

The early stages of tumor cell migration are difficult to detect. Invading
cells can follow myelinated axons, the basement membranes of blood vessels or
other basement membrane-like structures, as well as the perivascular space.
Invasiveness does not always correlate with degree of malignancy. Low-grade
astrocytomas, for example, sometimes infiltrate extensively. Migration of
cells from high-grade gliomas, however, often occurs more rapidly. When a
glioma is removed a new tumor generally forms within a few centimeters of the
original tumor mass, but satellite foci can develop at significantly greater
distances.

Invasiveness of brain tumors presents many problems for treatment. Even
radical resection (e.g. hemispherectomy) may leave behind migrating cells
that give rise to secondary tumor foci. Treatment of the core tumor mass by
radiation or chemotherapy is similarly problematic. In all these
interventions, a choice must be made between treating as large an area as
possible around the tumor and preserving quality of life for the patient.
One important example of this problem involves childhood brain tumors,
particularly primitive neuroectodermal tumors that arise during brain
development.

To understand how brain tumor dispersal can be controlled, we must determine
what causes tumor cells to migrate and investigate how migrating cells
interact with normal neurons, glia, and extracellular matrix (ECM). Several
kinds of cell-cell interactions may be critical, including gap-junctional
communication, neurotransmitter-mediated events, synaptic disruption, and
interactions with the immune system. It is likely that invading cells
misexpress genes that control cell migration during normal development and
also activate novel pathways that promote invasiveness. Examples of
candidate gene products that could control migration include specific motor
proteins, cytoskeletal elements, small GTPases that regulate interactions
between external signals and the cytoskeleton, cell surface receptors
involved in cell migration, proteases that remodel the ECM, ion channels that
induce changes in cell shape or volume, G protein-coupled receptors, and ECM
molecules produced by both tumor and surrounding normal cells. In addition
to understanding what causes dispersal, identifying the genes that control
the interrelated process of cell proliferation in migrating cells is also
important. These cells often exhibit transient cell cycle arrest, which
protects them from chemotherapy and radiation.

Determining the properties unique to invading brain tumor cells, and
understanding how these cells interact with normal brain elements will
suggest rational strategies for blocking tumor dispersal. For example, once
genes that promote or prevent migration have been identified, their
activities can potentially be modulated through strategies such as the use of
targeted antibodies, antisense oligonucleotides, siRNA, or the introduction
of specific exogenous genes or cells. The ultimate goal is to develop
interventions that block infiltration but cause minimal damage to adjacent
brain tissue. Such interventions could potentially transform brain tumor
into a manageable chronic disease.

Scope

Applications submitted in response to this PAS should focus on either: (1)
determining the causes of brain tumor dispersal; (2) understanding the
interactions of migrating tumor cells with normal brain elements; or (3)
developing interventions that target migrating tumor cells. Analysis of
either pediatric or adult brain tumors is appropriate. Studies that apply
insights from other fields (e.g. developmental neuroscience, glial cell
biology, stem or precursor cell biology) to the analysis of tumor spread are
within the scope of this PAS and are encouraged. Translational studies using
cell or animal models of brain tumor migration to test possible therapeutic
interventions are also encouraged. This PAS is intended to promote
interdisciplinary collaborations, as well as interactions between basic
scientists and clinicians. Possible areas of investigation include, but are
not limited to:

o Analysis of candidate genes and signal transduction pathways that control
brain tumor cell dispersal
o Genomic or proteomic expression profiling aimed at identifying novel genes
or proteins that control brain tumor cell dispersal
o Analysis of molecular and cellular mechanisms that control normal brain
cell migration and potentially regulate the dispersal of brain tumor cells
o Determination of the cells of origin and specific properties of migrating
brain tumor cells
o Analysis of the interactions of brain tumor cells with normal brain
elements that may contribute to understanding tumor dispersal
o Studies of extracellular matrix properties that potentially control normal
and aberrant migration of cells in the CNS
o Determination of what causes brain tumor cells to exit the cell cycle
during migration and reenter it during subsequent cell proliferation
o Studies of neural progenitor cell biology that may shed light on brain
tumor dispersal
o Investigation of why invading brain tumor cells are resistant to
chemotherapy or radiation
o Establishment of novel in vitro and in vivo migration assays that can be
used to elucidate mechanisms of brain tumor cell dispersal. Brain slice or
whole animal models in which tumor cells can be studied as they move through
the normal CNS are particularly encouraged.
o Development of novel methodologies that permit more effective visualization
of migrating brain tumor cells
o Development of therapeutic interventions that target migrating brain tumor
cells and prevent them from forming new tumors. These could include
targeting immune cells towards migrating tumor cells, introducing therapeutic
genes or cells expressing such genes, using chemoattractants to bring tumor
cells back to the main tumor mass, or other novel strategies.

MECHANISMS OF SUPPORT

This PAS will use the NIH research project grant (R01) and
exploratory/developmental grant (R21) award mechanisms. As an applicant, you
will be solely responsible for planning, directing, and executing the proposed
project. The proposed project period during which the research will be
conducted should adequately reflect the time required to accomplish the stated
goals and should be no more than 5 years for R01 grants. Applicants are
encouraged to contact program staff for advice about choosing the appropriate
grant mechanism.

R21 grants are one-time awards intended to encourage new
exploratory/developmental research projects by providing support for the
early stages of their development. For example, such projects could assess
the feasibility of a novel area of investigation or a new experimental system
that has the potential to enhance health-related research. These studies may
involve considerable risk but may lead to a breakthrough in a particular
area, or to the development of novel techniques, agents, methodologies,
models or applications that could have major impact on a field of biomedical,
behavioral, or clinical research.

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

R21 applications may request a project period of up to two years with a
combined budget for direct costs of up $275,000 for the two year period. For
example, you may request $100,000 in the first year and $175,000 in the
second year. The request should be tailored to the needs of your project.
Normally, no more than $200,000 may be requested in any single year. For
further information on the R21 mechanism, including Institute-specific
information, see
http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html

This PAS uses just-in-time concepts. It also uses the modular 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 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
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.

Competing continuation applications submitted in response to this PAS will
compete with all investigator-initiated applications and be referred and
reviewed according to the customary peer review procedures. Responsibility
for the planning, direction, and execution of the proposed project will be
solely that of the applicant. The earliest anticipated award date is April 1,
2005.

FUNDS AVAILABLE

NINDS has set aside $1,000,000 in total costs per year for applications sent
in response to this PAS. This is in addition to funds available for
applications that score within the NINDS payline (see NINDS Funding Strategy
http://www.ninds.nih.gov/funding/ninds_funding_strategy.htm) and depends on
the overall scientific merit of the applications and the availability of
funds throughout the duration of this solicitation (3 years). NCI will
consider programmatic priority, as reflected in this PAS, and scientific
merit in making funding decisions regarding applications assigned to it in
response to this PAS. Applications submitted in response to this PAS will
compete with all investigator-initiated applications for funding.

The total project period for an application submitted in response to this PAS
may not exceed 5 years. Because the nature and scope of the research proposed
may vary, it is anticipated that the size of each award will also vary.
Although the financial plans of the Institute provide support for this
program, awards pursuant to this PAS are contingent upon the availability of
funds and the receipt of a sufficient number of meritorious applications. At
this time, it is not known if this PAS will be reissued.

ELIGIBLE INSTITUTIONS

You may submit (an) application(s) if your institution has any of the
following characteristics:

o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges, hospitals,
and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic or foreign institutions/organizations

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry
out the proposed research is invited to work with their institution to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH programs.

SPECIAL REQUIREMENTS

Grantees will be required to attend at least one meeting per year that
fosters collaboration among basic neuroscientists, developmental
neuroscientists, neuroimmunologists, neurologists, neurosurgeons, and neuro-
oncologists and facilitates the bidirectional translation of basic and
clinical results. Attendance at these meetings must be described in annual
progress reports.

Plan for Dissemination of Data and Biomaterials

Sharing of biomaterials, data, and software in a timely manner is essential
for rapid progress in biomedical research. All applicants who respond to
this PAS must propose plans for sharing data and biomaterials generated
through the grant. PHS policy requires that investigators make unique
research resources available for research purposes to qualified individuals
within the scientific community when they have been published (see the NIH
Grants Policy Statement at
http://grants.nih.gov/grants/guide/notice-files/not96-184.html).
In addition, NIH recently released a statement on the sharing of research
data that applies to all investigator-initiated applications with direct
costs greater than $500,000 in any single year
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html).

The Initial Review Group will evaluate the proposed sharing plan and comment
on its adequacy in an administrative note in the summary statement.
Reviewers will not factor the proposed data-sharing plan into the
determination of scientific merit or priority score. The adequacy of the
plan will be considered by NIH staff in determining whether the grant shall
be awarded. The sharing plan as approved, after negotiation with the
applicant when necessary, will be a condition of the award.

WHERE TO SEND INQUIRIES

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

Direct inquiries regarding scientific/research issues to:

Dr. Robert Finkelstein
NINDS
Neuroscience Center, Rm 2143
6001 Executive Blvd.
Bethesda, MD 20892-9527
Telephone: (301) 496-5745
FAX: (301) 401-1501
Email: finkelsr@ninds.nih.gov

Dr. Steven Krosnick
NCI
Clinical Grants and Contracts Branch
Cancer Therapy Evaluation Program
Division of Cancer Treatment and Diagnosis
6130 Executive Blvd, EPN 7009
Bethesda, MD 20892
Telephone: (301) 496-8866
FAX: (301) 480-4663
Email: krosnicks@mail.nih.gov

Direct inquiries regarding financial or grants management matters to:

Ms. Kathleen Howe
Grants Management Branch
NINDS
6001 Executive Boulevard, Rm 3266
Bethesda, MD 20892
Telephone: (301) 496-7392
Email: howek@ninds.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
in 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.

SUPPLEMENTARY INSTRUCTIONS: All instructions for the PHS 398 (rev. 5/2001)
must be followed, with these exceptions:

o Research Plan

For R21 applications only, items a – d of the Research Plan (Specific Aims,
Background and Significance, Preliminary Studies, and Research Design and
Methods) may not exceed a total of 15 pages. No preliminary data is required
for R21 proposals, but may be included if it is available. Please note that
a Progress Report is not needed for R21 awards; competing continuation
applications for an exploratory/developmental grant will not be accepted.

Appendix. Use the instructions for the appendix detailed in the PHS 398
except that for R21 applications, no more than 5 manuscripts, previously
accepted for publication, may be included.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications requesting
up to $250,000 per year in direct costs must be submitted in the 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.

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 received by or 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 PAS 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 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 PAS will be assigned on the basis of
established PHS referral guidelines. An appropriate scientific review group
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 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. 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.

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 do they advance scientific knowledge? 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 $500,000 or more 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.

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 AMENDMENT "NIH
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research - Amended, October, 2001," published in the NIH Guide for Grants and
Contracts on October 9, 2001
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm .
The amended policy incorporates: the use of an NIH
definition of clinical research; updated racial and ethnic categories in
compliance with the new OMB standards; clarification of language governing
NIH-defined Phase III clinical trials consistent with the new PHS Form 398;
and updated roles and responsibilities of NIH staff and the extramural
community. The policy continues to require for all NIH-defined Phase III
clinical trials that: a) all applications or proposals and/or protocols must
provide a description of plans to conduct analyses, as appropriate, to
address differences by sex/gender and/or racial/ethnic groups, including
subgroups if applicable; and b) investigators must report annual accrual and
progress in conducting analyses, as appropriate, by sex/gender and/or
racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:
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 PAS 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
PAS 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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