THE ETIOLOGY, PATHOGENESIS AND TREATMENT OF ALS
RELEASE DATE: August 8, 2003
RFA Number: RFA-NS-04-003
Department of Veteran's Affairs (VA)
(http://www.va.gov/resdev/)
National Institute of Neurological Disorders and Stroke (NINDS)
(http://www.ninds.nih.gov/)
The Amyotrophic Lateral Sclerosis Association (ALSA)
(http://www.alsa.org)
CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.853 (NINDS)
LETTER OF INTENT RECEIPT DATE: September 30, 2003
APPLICATION RECEIPT DATE: October 22, 2003
THIS RFA CONTAINS THE FOLLOWING INFORMATION
o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations
PURPOSE OF THIS RFA
With this Announcement, the Department of Veterans Affairs (VA), the
National Institute of Neurological Disorders and Stroke (NINDS) and the
Amyotrophic Lateral Sclerosis Association (ALSA) invite research grant
applications that address the etiology, pathogenesis and treatment of
Amyotrophic Lateral Sclerosis.
RESEARCH OBJECTIVES
Amyotrophic lateral sclerosis (ALS) is a devastating disorder in which
those motor neurons that control voluntary movement are progressively
lost while those that subserve other functions such as cognition and
sensation are spared. At this time victims have no effective treatment
options; 50% die within three years of symptom onset and 80-90% within
five years.
ALS most likely represents a syndrome of very closely related disorders
resulting from numerous causes. Although degeneration may start in
either lower (spinal) or upper (cortico-spinal) motor neurons, both
populations of neurons eventually become involved. Cytologically,
neurons exhibit loss of dendrites, derangement of the cytoskeleton and
accumulation of a variety of proteins, some of which may form inclusion
bodies. Muscular atrophy occurs secondary to denervation; some degree
of peripheral reinnervation has been observed relatively early in the
course of the disease but the extent is markedly less than that observed
in other motor neuropathies. The disease is strikingly specific for
motor neurons; indeed one of the many tragedies of ALS is that patients
suffer with their sensory, cognitive, and emotional faculties
essentially unaffected.
ALS has a complex and incompletely understood etiology. Approximately 5
- 10% of cases have another affected family member (fALS) but in the
majority of cases the underlying cause and primary pathogenic mechanism
remain unknown. While each series of cases has a distinct presentation,
there is reason to believe that all cases can provide information
concerning common or convergent pathogenic mechanisms relevant to
sporadic ALS (sALS). Furthermore, new analytic methodologies can
identify genetic factors that affect traits other than risk that may be
important in sporadic ALS (e.g. rate of progression, site of onset).
Notwithstanding the opportunities presented by the study of genetic
forms of the disease, it is clear that ALS is in most cases a
multifactorial disorder triggered by as yet unknown factors, including
exposure to toxicants in the environment (either alone or in combination
with specific genetic factors). Incidence and prevalence are observed
to be generally uniform worldwide. While specific toxicants have been
studied for decades in an isolated, at-risk population in the Western
Pacific, recent reports have identified an approximately two-fold
increase in the risk of developing ALS among military personnel deployed
to SW Asia during the period of the Gulf War (Aug '90 to Jul '91)
relative to non-deployed personnel.
Four broad classes of pathogenic mechanisms are hypothesized to produce
the cellular dysfunction and death that produce the clinical syndrome of
ALS: 1) mitochondrial dysfunction/oxidative stress; 2) altered/disrupted
protein processing; 3) excitotoxicity/altered calcium homeostasis; and
4) altered cytoskeletal function/axonal transport. While these
hypotheses focus on motor neurons as the final common pathway of the
expression of ALS, there is increasing recognition of the contributions
of non-neuronal cells to the pathogenesis of ALS. These may represent
novel opportunities to develop therapeutic strategies to address more
"upstream" events in the primary pathophysiologic cascade or to
ameliorate the effects of secondary pathogenic processes.
At present there is no effective treatment for ALS. However, because
spinal motor neurons extend beyond the blood brain barrier, they may be
accessible to therapies that are not feasible for other neurons in the
CNS. Alternatively, recent advances in neurobiology may allow the
development of strategies to promote re-innervation of muscle.
Regardless, the development of novel strategies and technologies for the
development and delivery of therapeutics remains an important goal in
ALS research.
In summary, there remain important gaps in our understanding of the
continuum of pathogenesis, pathophysiology, treatment and prevention of
ALS. Accordingly, the NINDS, VA and ALSA have formed a public/private
partnership to solicit applications to support research in three general
lines of investigation: causative factors, pathobiology of motor neurons
and associated cell types and the diagnosis and treatment of ALS.
Specific topics include, but are not limited to:
o Epidemiology Sporadic ALS constitutes the great majority of typical
ALS but we do not have an adequate understanding of non-genetic risk
factors. Identifying specific genetic and environmental causes
typically requires large-scale, long-term, incidence-based studies that
are not feasible with the resources available in this initiative.
However, several strategies of lesser scope may be feasible including:
studies that focus on candidate toxicants (glutamate and glutamate
analogues, those relevant to the neuromuscular system, mitochondrial
inhibitors, etc.), studies that focus on populations at elevated risk,
data mining of existing databases or the development of epidemiologic
resources such as a national case control series.
o Genetic Factors Studies that focus on the interactions of genes with
other genes and/or environmental factors are of particular interest.
Appropriate topics include studies of genetic background effects (i.e.,
strain surveys, crosses with important other genetically modified mice,
etc.), environmental interactions (non-mammalian systems present
opportunities to study topics such as infectious agents as triggers and
putative environmental toxicants), and the biologic basis of age-
dependent motor neuron vulnerability. Classic gene discovery efforts are
supported by complementary, ongoing efforts and will not be considered
responsive to this RFA.
o Cell / Cell Interactions Despite the increasing awareness that ALS
is not a disorder of cell autonomous death, our understanding of the
signaling between the cell types involved or even the certain
identification of the cell types involved is relatively rudimentary.
Other important considerations include the switch from protective to
pathogenic contributions, the interaction between neuronal oxidative
stress and cytokines elaborated by non-neuronal cells. Mice with genes
expressed (or deleted) in a cell-specific manner may be particularly
informative in this regard.
o Cellular and Organellar Dysfunction Notwithstanding contributions
from other cell types, ALS is ultimately the expression of motor neuron
death and dysfunction resulting from incompletely understood mechanisms
(including upstream activators, non-apoptotic contributions of
mitochondrial pathology, endoplasmic reticulum stress, etc). There is
also a re-emerging appreciation of the axon as an early pathological
target in ALS. Recent advances in our understanding of axonal transport
and axonal responsiveness to trophic factors may provide new
opportunities to investigate pathogenesis in order to develop therapies
and restorative strategies.
o Protein and Molecular Dysfunction As discussed above, four general
classes of pathogenic processes have been observed in patients and
animal models. A better understanding of the contribution of each of
these processes to the course of the disease may provide opportunities
to alter the course of ALS. Other, new opportunities also include
alterations in metal handling (Zn2+, effects of metallothionein
knockouts), altered axonal transport and the question of whether
aggregates are pathogenic or protective.
o Novel Approaches to Delivery of Therapeutic Agents Spinal motor
neurons may be uniquely unconstrained by the blood-brain barrier,
nonetheless delivery of therapeutics remains a challenge and new
approaches are clearly indicated. These may entail strategies directly
targeting the neuron (specifically/receptor mediated or non-
specifically/endocytic) or by exploiting motor neurons' close functional
relationship with other cell types (e.g. muscle as a reservoir).
o Biomarkers - Biomarkers are critical for early disease detection and
more efficient clinical trials. Genomic, proteomic, metabolomic and
other novel techniques may be very powerful in the search for
biomarkers.
MECHANISM OF SUPPORT
This public/private partnership involves the research programs of the
VA, NINDS and the ALSA. Applications are solicited from VA-based
research laboratories, academic-based laboratories and other research
enterprises. The RFA will use both VA and NIH award mechanisms: VA
Merit Review Awards http://www.va.gov/resdev/directive/mrs.cfm ($500,000
direct cost over two years, no indirect costs) for VA-eligible research
laboratories and NIH R21 Awards ($275,000 direct cost over two years,
standard NIH indirect costs) for academic-based and other research
laboratories.
(See http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html)
As an applicant you will be solely responsible for planning, directing,
and executing the proposed project. This RFA is a one-time
solicitation. Future unsolicited, competing-continuation applications
based on this project will compete with all investigator-initiated
applications and will be reviewed according to the customary peer review
procedures at VA and the NIH. The anticipated award date is March 2004.
Applications that are not funded in the competition described in this
RFA may be resubmitted as NEW investigator-initiated applications at
either the VA or NIH using the standard guidelines and receipt dates for
NEW applications.
This RFA uses just-in-time concepts. It also uses the modular budgeting
format for R21 awards. (see
http://grants.nih.gov/grants/funding/modular/modular.htm).
Specifically, if you are submitting an R21 application, use the modular
format. This program does not require cost sharing as defined in the
current NIH Grants Policy Statement at
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.
FUNDS AVAILABLE
Together, the participating organizations intend to commit a total of
approximately $2.4 million in FY 04 to fund approximately 10 new grants
in response to this RFA. An applicant may request a project period of
up to 2 years and a budget for direct costs of up to $275,000 over the
course of two years for NIH awards or a budget for direct costs of up to
$500,000 over the course of two years for VA awards. This RFA is
considered to be a VA special initiative and is open to all eligible VA
investigators, regardless of their current VA funding. VA-eligible
investigators selected for non-VA funding will be allowed to resubmit
their budget to meet the NIH budgetary restrictions above (see "SPECIFIC
INSTRUCTIONS FOR VA GRANT APPLICATIONS"). Although the financial plans
of the participating institutions provide support for this program,
awards pursuant to this RFA are contingent upon the availability of
funds and the receipt of a sufficient number of meritorious
applications.
ELIGIBLE INSTITUTIONS
You may submit (an) application(s) if your institution has any of the
following characteristics:
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges,
hospitals, and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
o Domestic or foreign
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.
Individuals wishing to apply for VA funding must meet all VA eligibility
criteria. VA Central Office will verify the eligibility of all
investigators applying for VA funding prior to review.
SPECIAL REQUIREMENTS
The sponsoring organizations have issued several solicitations in areas
with significant intellectual or technical overlap with the current
proposals. In order to preserve the focus of each initiative,
applications will not be considered responsive to this RFA if their
principal focus is:
o Translational Studies including high throughput drug screens in
disease models i.e. applications responsive to PAR-02-139 (NINDS
Cooperative Program in Translational Research), PAR-02-138 (NINDS
Exploratory/Developmental Projects in Translational Research) or
NOT-NS-03-003 (NINDS Administrative Supplements: Testing of Candidate Drug
Treatments for Neurodegeneration in Rodent Models)
o Gene Discovery in human populations, i.e. applications responsive to
PAS-03-092 (Gene Discovery for Complex Neurological and Neurobehavioral
Disorders)
o DNA Repositories or Patient registries, i.e. applications responsive
to NOT-NS-02-012 (Human Genetic Resource Center: DNA and Cell Line
Repository) or NOT-NS-02-002 (Genetic Resource Center)
WHERE TO SEND INQUIRIES
We encourage inquiries concerning this RFA and welcome the opportunity
to answer questions from potential applicants. Inquiries may fall into
three areas: scientific/research, peer review, and financial or grants
management issues:
o Direct your questions about scientific/research issues to:
Paul A. Sheehy, Ph.D.
Neurodegeneration Cluster
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd, Rm. 2214A
Rockville, MD 20892-9525
(301) 496-5329 (v)
(301) 480-1080 (f)
sheehyp@ninds.nih.gov
William J. Goldberg, PhD
Medical Research Service (121E)
Department of Veteran's Affairs
1400I St., NW
Washington, DC 20005
(202) 408-3611 (v)
(202) 275-6100 (f)
william.goldberg@hq.med.va.gov
o Direct your questions about peer review issues to:
Alan Willard, Ph.D.
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd, Rm. 3208
Rockville, MD 20892-9529 (for courier service)
(301) 496-9223 (v)
(301) 402- 0182 (f)
willarda@ninds.nih.gov
o Direct your questions about financial or grants management matters to:
Michael Loewe
Grants Management Officer
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd, Rm. 3258
Rockville, MD 20892-9525
(301) 496-9231 (v)
(301) 402-4370 (f)
loewem@ninds.nih.gov
William J. Goldberg, PhD
Medical Research Service (121E)
Department of Veteran's Affairs
1400I St., NW
Washington, DC 20005
(202) 408-3611 (v)
(202) 275-6100 (f)
william.goldberg@hq.med.va.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:
Paul A. Sheehy, Ph.D.
Neurodegeneration Cluster
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd, Rm. 3208
Rockville, MD 20892-9525
(301) 496-5329 (v)
(301) 480-1080 (f)
sheehyp@ninds.nih.gov
SUBMITTING AN APPLICATION
All applications must be prepared using the PHS 398 research grant
application instructions and forms (rev. 5/2001). 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) 710-0267, Email: GrantsInfo@nih.gov.
SUPPLEMENTAL INSTRUCTIONS: The Research Plan section in applications for
both NIH and VA awards may not exceed 15 pages. No appendices are
permitted. Applications for NIH awards should use the modular budget
format (see "SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS").
Applications for VA awards will initially also use the NIH modular
budget format (see "SPECIFIC INSTRUCTIONS FOR VA GRANT APPLICATIONS").
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: NIH applications
requesting up to $275,000 direct cost over two years must be submitted
in a modular grant format. The modular grant format simplifies the
preparation of the budget in these applications by limiting the level of
budgetary detail. Applicants request direct costs in $25,000 modules.
Section C of the research grant application instructions for the PHS 398
(rev. 5/2001) at http://grants.nih.gov/grants/funding/phs398/phs398.html
includes step-by-step guidance for preparing modular grants. Additional
information on modular grants is available at
http://grants.nih.gov/grants/funding/modular/modular.htm.
SPECIFIC INSTRUCTIONS FOR VA GRANT APPLICATIONS: Investigators eligible
to apply for VA funding ($500,000 direct cost over two years, no
indirect costs) should indicate their VA Medical Center as the academic
institution and obtain the appropriate signatures. For the purpose of
initial processing, the application submitted should include a modular
budget of up to $250,000 per year for two years prepared according to
the PHS 398 format (see above). Those selected for funding will be
required to revise and resubmit budgets prepared on VA Merit Review
budget forms 10-1313-3 and 10-1313-4.
VA investigators who submit for VA funding may be selected for non-VA
funding. If so, they will be requested to submit a revised cover page
indicating their academic institution and appropriate signatures. VA
investigators selected for non-VA funding will also be requested to
revise and resubmit their budget to meet the NIH budgetary restrictions
for this RFA ($275,000 direct cost over two years, in $25,000 modules,
plus standard NIH indirect costs). It is anticipated that such awards
will be rare.
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev.
5/2001) application form must be affixed to the bottom of the face page
of the application. Type the RFA number on the label. Failure to use
this label could result in delayed processing of the application such
that it may not reach the review committee in time for review. In
addition, the RFA title and number must be typed on line 2 of the face
page of the application form and the YES box must be marked. The RFA
label is also available at:
http://grants.nih.gov/grants/funding/phs398/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 copies of the application must
be sent to:
Alan Willard, Ph.D.
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd, Rm. 2214A
Rockville, MD 20892-9525 (for courier service)
(301) 496-9223 (v)
(301) 402- 0182 (f)
willarda@ninds.nih.gov
APPLICATION PROCESSING: Applications must be received on or before the
application receipt date listed in the heading of this RFA. If an
application is received after that date, it will be returned to the
applicant without review.
Although there is no immediate acknowledgement of the receipt of an
application, applicants are generally notified of the review and funding
assignment within 8 weeks.
The Center for Scientific Review (CSR) will not accept any application
in response to this RFA that is essentially the same as one currently
pending initial review, unless the applicant withdraws the pending
application. However, when a previously unfunded application,
originally submitted as an investigator-initiated application, is to be
submitted in response to an RFA, it is to be prepared as a NEW
application. That is the application for the RFA must not include an
Introduction describing the changes and improvements made, and the text
must not be marked to indicate the changes. While the investigator may
still benefit from the previous review, the RFA application is not to
state explicitly how.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR
and responsiveness by the VA and the NINDS. Incomplete applications
will be returned to the applicant without further consideration. And,
if the application is not responsive to the RFA, NIH staff may contact
the applicant to determine whether to return the application to the
applicant or submit it for review in competition with unsolicited
applications at the next appropriate NIH review cycle.
Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate peer
review group convened by the sponsoring organizations 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 process in which only those applications deemed to have the
highest scientific merit, generally the top half of the applications
under review, will be discussed and assigned a priority score
o Receive a second level review by an appropriate National Advisory
Council or Board.
REVIEW CRITERIA
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.
In the written comments, reviewers will be asked to 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: September 30, 2003
Application Receipt Date: October 22, 2003
Peer Review Date: December 2003
Council Review: February 2004
Earliest Anticipated Start Date: March 1, 2004
AWARD CRITERIA
Award criteria that will be used to make award decisions include:
o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.
REQUIRED FEDERAL CITATIONS
HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that
applications and proposals involving human subjects must be evaluated
with reference to the risks to the subjects, the adequacy of protection
against these risks, the potential benefits of the research to the
subjects and others, and the importance of the knowledge gained or to be
gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm
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 and Safety Monitoring,
NIH Guide for Grants and Contracts, June 12, 1998:
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy
of the NIH that women and members of minority groups and their sub-
populations must be included in all NIH-supported clinical research
projects unless a clear and compelling justification is provided
indicating that inclusion is inappropriate with respect to the health of
the subjects or the purpose of the research. This policy results from
the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43).
All investigators proposing clinical research should read the "NIH
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research - Amended, October, 2001," published in the NIH Guide for
Grants and Contracts on October 9, 2001
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of
clinical research; updated racial and ethnic categories in compliance
with the new OMB standards; clarification of language governing NIH-
defined Phase III clinical trials consistent with the new PHS Form 398;
and updated roles and responsibilities of NIH staff and the extramural
community. The policy continues to require for all NIH-defined Phase
III clinical trials that: a) all applications or proposals and/or
protocols must provide a description of plans to conduct analyses, as
appropriate, to address differences by sex/gender and/or racial/ethnic
groups, including subgroups if applicable; and b) investigators must
report annual accrual and progress in conducting analyses, as
appropriate, by sex/gender and/or racial/ethnic group differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN
SUBJECTS: The NIH maintains a policy that children (i.e., individuals
under the age of 21) must be included in all human subjects research,
conducted or supported by the NIH, unless there are scientific and
ethical reasons not to include them. This policy applies to all initial
(Type 1) applications submitted for receipt dates after October 1, 1998.
All investigators proposing research involving human subjects should
read the "NIH Policy and Guidelines" on the inclusion of children as
participants in research involving human subjects that is available at
http://grants.nih.gov/grants/funding/children/children.htm
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH
policy requires education on the protection of human subject
participants for all investigators submitting NIH proposals for research
involving human subjects. You will find this policy announcement in the
NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of
research on hESCs can be found at http://stemcells.nih.gov/index.asp and
at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the NIH Human
Embryonic Stem Cell Registry will be eligible for Federal funding (see
http://escr.nih.gov). It is the responsibility of the applicant to
provide, in the project description and elsewhere in the application as
appropriate, the official NIH identifier(s)for the hESC line(s)to be
used in the proposed research. Applications that do not provide this
information will be returned without review.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT:
The Office of Management and Budget (OMB) Circular A-110 has been
revised to provide public access to research data through the Freedom of
Information Act (FOIA) under some circumstances. Data that are (1)
first produced in a project that is supported in whole or in part with
Federal funds and (2) cited publicly and officially by a Federal agency
in support of an action that has the force and effect of law (i.e., a
regulation) may be accessed through FOIA. It is important for
applicants to understand the basic scope of this amendment. NIH has
provided guidance at
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this PA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application
should include a description of the archiving plan in the study design
and include information about this in the budget justification section
of the application. In addition, applicants should think about how to
structure informed consent statements and other human subjects
procedures given the potential for wider use of data collected under
this award.
STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:
The Department of Health and Human Services (DHHS) issued final
modification to the "Standards for Privacy of Individually Identifiable
Health Information", the "Privacy Rule," on August 14, 2002. The
Privacy Rule is a federal regulation under the Health Insurance
Portability and Accountability Act (HIPAA) of 1996 that governs the
protection of individually identifiable health information, and is
administered and enforced by the DHHS Office for Civil Rights (OCR).
Those who must comply with the Privacy Rule (classified under the Rule
as "covered entities") must do so by April 14, 2003 (with the exception
of small health plans which have an extra year to comply).
Decisions about applicability and implementation of the Privacy Rule
reside with the researcher and his/her institution. The OCR website
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule,
including a complete Regulation Text and a set of decision tools on "Am
I a covered entity?" Information on the impact of the HIPAA Privacy
Rule on NIH processes involving the review, funding, and progress
monitoring of grants, cooperative agreements, and research contracts can
be found at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.
URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and
proposals for NIH funding must be self-contained within specified page
limitations. Unless otherwise specified in an NIH solicitation, Internet
addresses (URLs) should not be used to provide information necessary to
the review because reviewers are under no obligation to view the
Internet sites. Furthermore, we caution reviewers that their anonymity
may be compromised when they directly access an Internet site.
HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of
"Healthy People 2010," a PHS-led national activity for setting priority
areas. This RFA is related to one or more of the priority areas.
Potential applicants may obtain a copy of "Healthy People 2010" at
http://www.health.gov/healthypeople.
AUTHORITY AND REGULATIONS: This program is described in the Catalog of
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject
to the intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review. Awards are made under the authorization
of Sections 301 and 405 of the Public Health Service Act as amended (42
USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR
Parts 74 and 92. All awards are subject to the terms and conditions,
cost principles, and other considerations described in the NIH Grants
Policy Statement. The NIH Grants Policy Statement can be found at
http://grants.nih.gov/grants/policy/policy.htm.
The PHS strongly encourages all grant recipients to provide a smoke-free
workplace and discourage the use of all tobacco products. In addition,
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in
certain facilities (or in some cases, any portion of a facility) in
which regular or routine education, library, day care, health care, or
early childhood development services are provided to children. This is
consistent with the PHS mission to protect and advance the physical and
mental health of the American people.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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