THERAPEUTIC OPPORTUNITIES IN PROGRESSIVE STAGES OF SPINAL CORD INJURY
 
RELEASE DATE:  August 14, 2003
 
RFA Number:  RFA-NS-04-004
 
National Institute of Neurological Disorders and Stroke (NINDS) 
 (http://www.ninds.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.853
 
LETTER OF INTENT RECEIPT DATE:  November 24, 2003

APPLICATION RECEIPT DATE:  December 23, 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 Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA 

The National Institute of Neurological Disorders and Stroke (NINDS) 
invites applications for basic studies that define therapeutic 
opportunities during the progressive stages of spinal cord injury (SCI) 
from acute through chronic time points.  Although numerous 
neuroprotective and repair strategies have been identified that improve 
anatomical or functional outcome after SCI in animal models, the causal 
relationship between cellular or anatomical findings and functional 
outcomes has not been established.  This RFA seeks research to 1) 
elucidate the mechanisms that underlie recovery induced by 
neuroprotection or repair strategies in animal models, 2) define 
progressive changes in acute, subacute or chronic stages after SCI that 
influence cell survival, regeneration, sprouting and/or recovery of 
function, 3) target therapeutic strategies in animal models to 
clinically-relevant stages and types of SCI, based on known 
pathophysiological processes, anatomical or functional/clinical 
outcomes.
  
RESEARCH OBJECTIVES
 
Background

A quarter of a million Americans are living with functional deficits 
due to chronic SCI and over 10,000 new cases occur in the U.S. each 
year.  Traumatic SCI occurs suddenly but the physiological and 
functional changes initiated by the injury progress with time.  This 
progression includes a period of "secondary injury" characterized by 
immunological reactions, scarring, continuing cell death and cavitation 
as well as ongoing functional changes in spinal circuitry.  Substantial 
recovery of function near or below the level of injury is seen after 
most incomplete SCI, which may continue for months to years, and can be 
facilitated by rehabilitation.  Most patients with complete SCI show 
substantially less spontaneous recovery but also undergo continuing 
neurological changes that may lead to development of spasticity, 
autonomic dysreflexia, pain and other complications.  To date, few 
basic science discoveries have been applied clinically to improve 
functional outcomes.  In recent years, however, an expanding community 
of SCI researchers has reported progress in developing intervention 
strategies in animal models.  Such strategies are reported to limit 
secondary injury and to enhance regeneration, functionally significant 
sprouting, and recovery of function.  It is important to assess the 
promise of these interventions with great care.  Human SCI is a complex 
and highly variable condition with functional deficits that greatly 
depend on the spinal level, severity of injury and the length of time 
since SCI occurred.  It is critical that studies now be designed to use 
animal models of SCI at appropriate spinal levels or stages to test 
therapeutic strategies.  This will improve the likelihood of success in  
translation of promising therapies to effective clinical therapies. 

The concept for this RFA was developed with input from two NINDS 
workshops, "Translating Promising Strategies for Spinal Cord Injury 
Therapy" (2003) and the "International Workshop on Brain Banking" 
breakout session on CNS Trauma (2002).  Participants identified issues 
that bear on future clinical trials, including prognosis in the absence 
of intervention, mechanism of injury, and timing of the intervention 
relative to the time course of secondary damage and changes in 
regenerative potential in the cord. They also noted the need to 
evaluate varied types of injury (location, extent and duration) and 
comparative time scales in animal models versus human injury.  
Evaluating the relevance of strategies that moderately affect 
locomotion in rodents requires recognition of the differences between 
rodent and human spinal circuitry and function, and species differences 
in SCI neuropathology.  In addressing recovery, progressive functional 
changes seen in people after SCI were described, and the need to 
explore such changes using animals to relate pathological processes or 
neural plasticity to functional recovery was stressed.  

Promising strategies for neuroprotection are evolving, including 
hypothermia, blockers of secondary injury (e.g., steroids and other 
anti-inflammatory agents, cord irradiation or manipulations of immune 
cells), and some cellular therapies.  Likewise, a number of strategies 
to promote regeneration have been identified, including application of 
growth factors and other growth promoting agents, stem cells, glial 
cells, myelin-inhibitor neutralization, extracellular matrix 
inhibition, and cell- or matrix-containing guidance channels.  Some of 
these are reported to promote remyelination.  Other strategies are 
based on activity-driven interventions.  Most of these studies report 
incremental improvement in anatomical and locomotor measures, but do 
not provide evidence that these measures are causally related.  
Information obtained by use of physiological measures, imaging and 
indicators of cell survival and function might significantly improve 
our understanding of the basis of reported functional restoration.  In 
addition, longer studies are needed to assess the persistence of any 
functional advantage of protective therapies.

A common component of effective therapies may be altering function by 
stimulating endogenous plasticity.  The functional importance of this 
plasticity, compared to that of regenerating axons, has been under-
emphasized in most reports citing anatomical and functional repair 
after application of regeneration strategies.  Research focused on 
assessing the basis of ongoing functional recovery is needed.  This 
natural recovery must also be adequately controlled for in studies 
aimed at identifying the mechanisms by which repair strategies promote 
recovery. 

The "window of opportunity" where repair strategies are effective has 
not been established preclinically.  To define which strategies could 
be advantageously used in acute and/or chronic injuries, more 
information is needed about the mechanism(s) of action of particular 
interventions.  Important questions include what the optimal timing of 
a treatment is, its duration, and when is there essentially no hope for 
recovery after SCI?  Until recently, almost all experimental strategies 
were applied acutely after SCI in rat models.  New research has shown 
that a one-to-two week delay in the application of some strategies 
leads to improved recovery in rodent models of incomplete SCI. The 
mechanism by which these delayed treatments improve functional outcomes 
is not known, and it is unlikely that this delay models chronic human 
SCI.  There is no definition of acute, subacute and chronic injury in 
animal models, nor is it known how the temporal progression of SCI in 
these models relates to corresponding stages of human injury.  Such 
considerations are essential to understanding the effects of the 
therapeutic strategies, and to improving translation of these 
strategies to clinical use.  Measures of anatomical changes alone are 
not sufficient, as behavioral recovery can be measured over many weeks, 
while lesion size is expanding in most experimental models.  Finally, 
validation of treatment strategies in non-rodent animal models could be 
needed to refine or confirm the efficacy of novel strategies for SCI 
repair.  When rodents do not adequately model human spinal circuitry or 
pathophysiology, non-rodent models should be utilized to establish 
relevance for human testing.  

Objectives and Scope

This initiative is based on recent reports that numerous cellular, 
pharmacological and gene-therapy strategies show promise for the 
protection and/or repair of the spinal cord after injury.  The 
"promise" is based largely upon evidence of tissue preservation, tract 
tracing and incremental recovery in behavioral measures.  Causal 
relationships between these measures are not clearly shown in these 
studies, and the therapeutic potential for application of these 
strategies is based more on conjecture than on information about 
specific opportunities for intervention in human SCI.  

This RFA seeks to address the need for information about the changing 
state of the spinal cord following injury in relation to 1) the 
potential for repair and the mechanisms that underlie recovery induced 
by neuroprotection or repair strategies in animal models, 2) acute, 
subacute or chronic stages after SCI that influence cell survival, 
regeneration, sprouting and/or recovery of function, 3) targeting of 
therapeutic strategies in animal models to specific clinically-relevant 
stages and types of SCI, based on known pathophysiological processes, 
anatomical or functional/clinical outcomes.  These questions are key 
prerequisites to translation of promising repair strategies to 
effective treatment of human SCI.  Applications for preclinical 
(animal) and human studies research are invited, however, no clinical 
trials will be considered.

Appropriate topics for investigation under this RFA would include but 
are not limited to: 

o   Characterization of the mechanism(s) of action of promising 
therapeutic strategies to determine if the treatment outcome is based 
on protection, regeneration, impact on circuits outside the lesion 
area, or other mechanisms.  Promising candidates include cellular, 
pharmacological, mechanical, genetic, activity-based or combined 
approaches that affect behavioral outcomes.

o   Studies to define the progression of therapeutic windows of 
opportunity following SCI by characterizing pathophysiological 
processes in animal models as they relate to behavioral outcomes and 
associated clinical outcomes.  Of particular interest: evidence of 
persistent primary demyelination, relationship of cavity expansion or 
cell death to loss of function, effects of ongoing inflammatory 
processes and endogenous plasticity or repair mechanisms on behavioral 
outcomes.

o   Studies to determine effective time of administration of a repair 
strategy, based on known mechanism(s) of action.  Species differences 
in the anatomy or function of circuits and relation to human pathology 
or behavior after SCI should be addressed.

o   Experimental protocols that incrementally test components of complex 
therapies to establish their critical contribution to functional 
recovery in appropriate animal models and stages of injury.

o   Utilization of tracing, imaging, or other technologies to detect the 
long-term fate of implanted cells, their migration and functional 
status following implantation into sites in or near regions of SCI.

o   Strategies to alter pathophysiological responses to injury in order 
to prolong or reinstate a window of opportunity for effective repair of 
the spinal cord. 

o   Studies to define progressive changes in barriers to regeneration and 
show under what circumstances targeted strategies that alter these 
processes can improve outcomes.

MECHANISM OF SUPPORT
 
This RFA will use NIH R01 award mechanism.  As an applicant you will be 
solely responsible for planning, directing, and executing the proposed 
project.  This RFA is a one-time solicitation.  Future unsolicited, 
competing-continuation applications based on this project will compete 
with all investigator-initiated applications and will be reviewed 
according to the customary peer review procedures.  The anticipated 
award date is July 2004.  Applications that are not funded in the 
competition described in this RFA may be resubmitted as NEW 
investigator-initiated applications using the standard receipt dates 
for NEW applications described in the instructions to the PHS 398 
application. 

This RFA uses just-in-time concepts.  It also uses the modular 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.  

FUNDS AVAILABLE
 
The NINDS intends to commit approximately $1.5 million in FY 2004 to 
fund three to four new and/or competitive continuation grants in 
response to this RFA.  An applicant may request a project period of up 
to five years and a budget for direct costs of up to $500,000 per year.  
Because the nature and scope of the proposed research will vary from 
application to application, it is anticipated that the size and 
duration of each award will also vary.  Although the financial plans of 
the NINDS provides 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

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.   
 
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:

Naomi Kleitman, Ph.D.
Program Director, Repair and Plasticity
National Institute of Neurological Disorders and Stroke 
6001 Executive Blvd., Room 2204, MSC 9525
Bethesda, MD  20892
Telephone:  (301) 496-1447
FAX: (301) 480-1080
Email: nk85q@nih.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., Room 3208
Bethesda, MD  20892
Telephone:  (301) 496-9223
FAX: (301) 402-0182
Email: aw135y@nih.gov

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

Michael J. Loewe
Chief, Grants Management Branch
National Institute of Neurological Disorders and Stroke 
6001 Executive Blvd., Suite 3290, MSC 9537
Bethesda, MD  20892-9537
Telephone:  (301) 496-9231
FAX: (301) 402-0219
Email: ml70m@nih.gov 

LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that 
includes the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does 
not enter into the review of a subsequent application, the information 
that it contains allows IC staff to estimate the potential review 
workload and plan the review.
 
The letter of intent is to be sent by the date listed at the beginning 
of this document.  The letter of intent should be sent to:

Naomi Kleitman, Ph.D.
Program Director, Repair and Plasticity
National Institute of Neurological Disorders and Stroke 
6001 Executive Blvd., Room 2204, MSC 9525
Bethesda, MD  20892
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 496-1447
FAX: (301) 480-1080
Email: nk85q@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 document is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an 
interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications 
requesting up to $250,000 per year in direct costs must be submitted in 
a modular grant format.  The modular grant format simplifies the 
preparation of the budget in these applications by limiting the level 
of budgetary detail.  Applicants request direct costs in $25,000 
modules.  Section C of the research grant application instructions for 
the PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-
by-step guidance for preparing modular grants.  Additional information 
on modular grants is available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 
5/2001) application form must be affixed to the bottom of the face page 
of the application.  Type the RFA number on the label.  Failure to use 
this label could result in delayed processing of the application such 
that it may not reach the review committee in time for review.  In 
addition, the RFA title and number must be typed on line 2 of the face 
page of the application form and the YES box must be marked. The RFA 
label is also available at: 
http://grants.nih.gov/grants/funding/phs398/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 and 
all copies of appendix material must be sent to:

Alan Willard, Ph.D.
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke 
6001 Executive Blvd., Room 3208
Bethesda, MD  20892
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 496-9223
FAX: (301) 402-0182
Email: aw135y@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 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 NINDS 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 the NINDS 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.

(1) SIGNIFICANCE:  If the aims of your application are achieved, how do 
they advance scientific knowledge or development of SCI therapy?  What 
will be the effect of your study on concepts or methods that help 
understand the mechanisms by which repair strategies restore function 
after SCI and facilitate translation of these treatment strategies to 
clinical use?  Do the proposed studies relate animal models to 
literature about or studies of human pathology, physiology or behavior 
after SCI?  

(2) APPROACH:  Are the conceptual framework, design, methods, and 
analyses adequately developed, well integrated, and appropriate to the 
aims of the project?  Is the time window in which a strategy is applied 
well justified and appropriate to potential future clinical 
application?  Is the course of natural recovery known and adequately 
controlled for?  Do you acknowledge potential problem areas and 
consider alternative tactics?  

(3) INNOVATION:  Does your project employ novel concepts, approaches or 
methods?  When existing therapeutic strategies are to be tested, is the 
proposed analysis of the strategies likely to produce new information 
important to application of that strategy toward treatment of human 
SCI?  Are the aims original and innovative?  Does your project develop 
new methodologies, animal models or technologies?

(4) INVESTIGATOR: Are you appropriately trained and well suited to 
carry out this work?  Is the work proposed appropriate to your 
experience level as the principal investigator and to that of other 
researchers (if any)?

(5) ENVIRONMENT:  Does the scientific environment in which your 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:  

(1) Relevance to human SCI:  Is the experimental design and any 
proposed therapeutic strategy justified in relation to measures of the 
timing of pathophysiological changes and/or natural recovery after 
human SCI?  Is the effective therapeutic window of the selected 
strategy likely to be translatable to clinical practice?

(2) Responsiveness to Objectives and Scope of this RFA as detailed in 
the Significance, Approach and Innovation sections above.

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: November 24, 2003
Application Receipt Date: December 23, 2003
Peer Review Date: March 2004
Council Review: May 2004
Earliest Anticipated Start Date: July 2004

AWARD CRITERIA

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

o Scientific merit (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

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 RFA 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.


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