EXPLORATORY/DEVELOPMENTAL TRANSLATIONAL GRANTS FOR BORDERLINE PERSONALITY

RELEASE DATE:  September 4, 2003

RFA Number:  RFA-MH-04-006

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATIONS

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

COMPONENTS OF PARTICIPATING ORGANIZATIONS

National Institute of Mental Health (NIMH)
 (http://www.nimh.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.242

LETTER OF INTENT RECEIPT DATE:  November 14, 2003
APPLICATION RECEIPT DATE:  December 18, 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

This is a reissue of RFA MH-03-001.

The National Institute of Mental Health (NIMH) reaffirms its commitment to 
encouraging cutting-edge research and promoting the development of new 
investigators in the area of borderline personality disorder (BPD), which has 
not received research attention commensurate with its significance as a public 
health problem.  In addition, based on the response to the previous Request for 
Applications (RFA), NIMH recognizes the potential of this extension of its 
translational research initiative to borderline personality for contributing to 
the desired research and correlated increase in research capacity.

The purpose of this RFA is to invite new and amended exploratory/developmental 
(R21) applications that propose translations of basic science theories, methods 
and findings to clinical research concerning borderline personality disorder; 
examining BPD features and its relationship to putative causal factors and to 
other disorders, constructs, and variables.

Applicants for exploratory/developmental R21 grants should be committed to 
pursuing the proposed line of research through subsequent research project 
grants (R01 or other appropriate grant mechanisms) using the outcome data 
obtained as a result of this RFA.  Translations may involve basic theories, 
methods, and/or findings from modern psychometrics and measurement theory, basic 
behavioral science, social science, and neuroscience.  The specific clinical 
research focus chosen by the applicant should reflect the potential for 
innovative, important, and scientifically sound translations to clinical 
research concerning borderline personality disorder.

RESEARCH OBJECTIVES

Borderline personality disorder (BPD) is a complex, serious, disabling disorder 
with significant mortality.  Although prevalent in clinical settings it has not 
received research attention commensurate with its significance.  Since only a 
small number of investigators have undertaken research concerning this disorder, 
the NIMH portfolio does not reflect this disorder's importance as a public 
health problem.  With few researchers working in an area of study, there are 
few opportunities for training and mentoring of new researchers, which in turn 
perpetuates the limited amount of research being conducted and NIMH grants 
awarded for this area of study.  Recently, several developments have occurred 
that offer the potential for increasing NIMH support for research concerned 
with BPD.

First, in 1999, the Borderline Personality Disorder Research Foundation (BPDRF) 
generated a significant increase in BPD research by initiating support for 
research centers concerned with BPD in the United States (US) and in Europe.  
Subsequently, the BPDRF has sought to encourage government research funders in 
the US and in Europe to increase their support for BPD research and to encourage 
early career researchers to undertake programs of research on BPD.  In support 
of those goals, in 2002, the BPDRF announced a grant program for individual 
investigators.  The first awards under this program were made in the spring of 
2003.

Second, several years ago, NIMH launched a translational research initiative to 
encourage the involvement of basic researchers and clinical scientists in the 
translation of basic science theories, methods, and findings into the clinical 
arena.  The number and quality of the resultant translational research 
applications has demonstrated the readiness and ability of the field to enhance 
the clinical research enterprise.  This RFA seeks to build on the two 
developments mentioned above:  1) increased research activity and interest 
concerning BPD that the BPDRF has generated; and 2) utilize the new energy and 
cutting edge methods that the Institute's translational research initiatives 
have brought to clinical research.  Specifically, this RFA seeks to extend the 
Institute's translational research initiatives to BPD research, and thereby 
bring cutting edge theories, methods, and findings from modern psychometrics 
and measurement theory, behavioral science, social science, and neuroscience to 
clinical research concerning BPD.  Such extensions offer considerable promise 
for enabling advances in better measurement and understanding of the 
complexities of this disorder and its core features - the pervasive 
instabilities in affect, interpersonal relationships, behavior, concept of self, 
and cognition(s); and the co-occurrence of BPD with other disorders (e.g., 
depression, post-traumatic stress disorder, and substance abuse).  Such 
extensions also offer the promise of developing and testing new science-based 
treatment models and procedures for use in the clinical setting.

The potential for extending NIMH's translational research initiative to BPD 
research and for involving more researchers, particularly early career 
investigators, was proposed in the summer of 2001 at the conference, "New 
Directions in Borderline Personality," at Rockefeller University that was co-
sponsored by NIMH and the BPDRF.  It was further explored in the early summer 
of 2002 at a follow-through conference, "New Directions in Borderline 
Personality II," that the University of Minnesota Department of Psychiatry 
hosted.  The number of applications submitted under the previous RFA (MH-03-001) 
and the potential of these applications has demonstrated that the field is 
interested and ready to extend translational research to BPD.

Some possibilities for translation of basic science include: modern 
psychometrics and measurement theory, basic behavioral science, social science, 
and neuroscience.  The exploratory/developmental grant mechanism is designed to 
enable researchers to develop procedures and data that will lead to the 
development of R01 applications.  Areas of research interest sought under this 
RFA encompass all aspects of BPD, including, but not limited to, better 
specification of the disorder and the criteria for diagnosis; determination of 
possible subtypes of BPD and their associated features and correlates; 
illumination of the role of gender, SES, and culture in the manifestation of the 
disorder; elucidation of the mechanisms of expression and moderation of the 
extreme temperament and behavioral traits that are presumed to account for this 
disorder; clarification of the relationship of BPD to other disorders and their 
mechanisms; identification of factors that are involved in the onset, 
escalation, and cessation of BPD features; development of more complete and 
accurate measurement of the pervasive instabilities of affect, interpersonal 
relationships, concept of self, behavior, and cognitions, and determination of 
factors involved in variations of time between extreme states, in the duration 
of extreme states, and in the moderation of expressions of extreme states of 
these features; the role of learning, biological factors, and the brain in the 
instabilities that characterize BPD; elucidation of factors that account for 
periods of self-injury and the mechanisms that support this type of behavior; 
and the development and preliminary testing of new treatment models and 
procedures that are based on translations of basic science.  The specific 
research focus should reflect the opportunity for the innovative and 
scientifically meritorious translation of basic science to advance BPD clinical 
research.

Applications submitted under this RFA must meet the six criteria presented below 
to be considered responsive.  Applicants should explicitly address each criteria 
in the narrative of the application.

1.  The proposed research must have as a major feature the translation 
(application) of basic science (theory, methods, or findings) to clinical 
research concerning BPD.

2.  The principal researchers for the proposed research must have substantial 
expertise in both the area of basic science from which the translation is to be 
made and in relevant clinical research.  Collaborations of basic and clinical 
scientists are encouraged.  Collaborating scientists need not be at the same 
institution, but in such cases, the procedures for achieving collaboration 
during the project must be specified.  Substantial expertise in the areas of 
science involved in the research is required so that the research team can look 
beyond the immediate research to other possibilities for translation and 
consider other clinical issues that might benefit from new basic research, and 
so that there can be broad training in translational research (see below).

3.  Consistent with the need to develop a cadre of translational researchers, 
the project must include provision for an advanced graduate student, a post doc, 
or an early career researcher to receive additional training in the basic 
science area from which the translation for the research project is drawn 
(e.g., in modern measurement theory for the translation of item response theory 
for developing a measure of a BPD latent construct) and similarly to receive 
training in the clinical science involved in the research.  The goal for this 
training is to prepare this person to initiate translational research.  The 
project budget must include provision for this training and a training plan must 
be briefly described.  The training may utilize various modalities, including 
courses, directed readings, tutorials, and visits to labs of other scientists, 
as well as active involvement in the proposed research as a collaborating junior 
colleague.

4.  The proposed research must have clear, immediate, and compelling relevance 
to the clinical phenomena of borderline personality disorder.  (It is 
anticipated that this requirement will most often be met by having persons who 
meet diagnostic criteria for BPD as the primary subjects.)

5.  The proposed research will be a new line of investigation for BPD, and so, 
consistent with the exploratory/developmental mechanism.  Preliminary data, 
while always desirable, is neither expected nor required.  The proposed research 
should be scientifically sound and the qualifications of the research team 
appropriate.  It is expected that funded projects will need to make adjustments 
based on their initial work, and the work plan and budget should provide for 
this.

6.  The principal researcher(s) of the team should be committed to pursuing this 
line of research beyond the exploratory/development grant period if the data 
developed with the R21 grant support this course.  The subsequent research that 
would proceed from the requested R21 grant support must be indicated.

Applicants are strongly encouraged to contact the NIH program staff listed under 
INQUIRIES with any questions regarding the responsiveness of their proposed 
project to the goals of this RFA.

Possible Research Topics

The following research areas are presented only as illustrations of possible 
topics.  The list is not intended to be comprehensive or restrictive.  The 
topics are expected to reflect the opportunities for new and innovative 
applications of basic science to BPD and its features:

o  The application of taxonomic science to BPD to explore the possibility of 
subtypes of BPD and shared and distinct biological, development, clinical, and 
social factors.  The DSM criteria for the diagnosis of BPD are that any 5 (or 
more) of 9 symptom criteria be met.  Thus, scores of diverse combinations of 
symptom criteria enable the diagnosis of this disorder, suggesting the 
possibility that the disorder is not homogenous but consists of two or more 
subtypes.  Identification of valid subtypes and their shared and distinct 
factors would advance diagnosis, treatment, and research.

o  The use of measurement theory and behavioral science to develop accurate, 
ongoing measures of one or more of the core features of BPD, e.g., instability 
in concept of self.  The availability of such measures could enhance the 
accuracy of diagnosis and evaluation of interventions and advance the study of 
factors associated with potentially important facets of instability such as 
variation in the time between extremes.  The availability of validated measures 
for two or more such features would enable research on the relationship of time 
variation in one to the other and the shared and unique factors associated with 
the expression of these features.

o  The use of systematic observations of behavior and emotions to determine 
patterns of dyadic interactions and to test learning theory, pharmacological and 
other intervention methods to determine the role of different approaches and 
factors in preventing the escalation of anger and aggression and in obtaining 
therapeutic change in interpersonal relationships.

o  The use of item response theory (irt) to develop items measuring the latent 
constructs of BPD that are not influenced by gender, socioeconomic status (SES), 
and culture/ethnicity, and thus reflect pure expressions.  And, conversely, to 
identify sets of items that reflect gender, SES and culture/ethnicity specific 
expressions of BPD so that the mechanisms by which these factors affect the 
differential expression of BPD symptoms can be investigated.

o  Application of methods and principles from affective neuroscience to explicate 
dimensions of mood and emotional response in BPD, employing standard paradigms 
for which normative data exist and recording multiple response systems in order 
to contribute to an integrative understanding of the biobehavioral organization 
of affect and/or social cognition in BPD.

o  Studies that attempt to define more precisely the relevant temperament and 
other biobehavioral dimensions relevant to BPD, and to specify which 
combinations of dimensional characteristics may contribute to subtypes, 
severity, or risks for disorder.  Such studies might employ designs that are 
intended to explore the full range of these dimensions by combining patient 
groups, non-clinical subjects at high risk or with elevated scores on screening 
questionnaires, and non-clinical subjects scoring low on screening measures.

o  The translation of new basic science findings to a new treatment model or 
procedure, and the development and preliminary testing of this approach.

MECHANISM OF SUPPORT

This RFA will use the NIH Exploratory/Developmental (R21) award mechanism.  An 
applicant may request a project period of up to 3 years and a budget for direct 
costs of up to $125,000 per year.  Direct costs of up to $150,000 per year may 
be requested to allow for facilities and administrative (F&A) costs on 
consortium arrangements.

Both new applications and amended ones that were submitted under the previous 
RFA may be submitted.  Amended applications should follow the standard 
guidelines as noted in the PHS 398 kit (including a 3 page introduction and 
marking text that has changed). 

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 August 1, 2004.

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

RESUBMISSION OF UNFUNDED APPLICATIONS

Applications that are not funded in the competition described in this RFA may be 
resubmitted as NEW investigator-initiated applications only, as described at 
NOT-OD-03-019 (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-019.html).  
These NEW applications must be submitted on the standard receipt dates 
(https://grants.nih.gov/grants/funding/submissionschedule.htm and will be 
expected to conform to the requirements of the standard NIH Exploratory/
Developmental Grant award mechanism, which limits the award to 2 years with a 
combined direct cost budget of up to $275,000 for the 2-year period (with no 
single year exceeding $200,000), as well as a 15-page research plan (see 
https://grants.nih.gov/grants/guide/pa-files/PA-03-107.html).

FUNDS AVAILABLE

The NIMH intends to commit approximately $1.2 million total cost in FY 2004 to 
fund up to eight new grants in response to this RFA.  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 NIMH 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 institutions/organizations
o  Faith-based or community-based organizations
o  Foreign institutions are not eligible to apply.

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 mental health scientific/research issues to:

James Breiling, Ph.D.
Division of Mental Disorders, Behavioral Research and AIDS
National Institute of Mental Health
6001 Executive Boulevard, Room 6179
Bethesda, MD  20892
Telephone:  (301) 443-3527
FAX:  (301) 443-4611
Email:  jbreilin@mail.nih.gov

o  Direct your questions about peer review issues to:

Michael Kozak, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6138, MSC 9608
Bethesda, MD  20892
Telephone:  (301) 443-1340
FAX:  (301) 443-4720
Email:  mkozak@nih.gov

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

Brian Albertini
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6135, MSC 9605
Bethesda, MD  20892-9625
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 443-0004
FAX:  (301) 443-6885
Email:  albertib2@mail.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 NIMH 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:

Dr. James Breiling
Division of Mental Disorders, Behavioral Research and AIDS (DMDBA)
National Institute of Mental Health
6001 Executive Boulevard, Room 6179
Bethesda, MD  20892
Telephone:  (301) 443 3527
FAX:  (301) 443 4611
Email:  jbreilin@mail.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 https://grants.nih.gov/grants/funding/phs398/phs398.html 
in an interactive format. For further assistance contact GrantsInfo, 
Telephone (301) 710-0267, Email: GrantsInfo@nih.gov.

PLEASE NOTE THAT THE RESEARCH PLAN IS LIMITED TO 15 PAGES.  APPENDIX MATERIAL IS 
LIMITED TO 5 ITEMS.

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

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

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

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application and all 
copies of the appendix material must be sent to:

Jean G. Noronha, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6154, MSC 9609
Bethesda, MD  20892-9663
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 443-3367
FAX:  (303) 443-4720
Email:  jnoronha@mail.nih.gov

APPLICATION PROCESSING:  Applications must be received by the application 
receipt date listed in the heading of this RFA.  If an application is received 
after that date, it will be returned to the applicant without review.

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 from the previous 
unfunded version of the application. 

PEER REVIEW PROCESS

Upon receipt, applications will be reviewed for completeness by CSR and 
responsiveness by the NIMH.  Incomplete and nonresponsive applications will not 
be reviewed.
  
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 NIMH in accordance with the review criteria stated below.  As part of the 
initial merit review, all applications will:

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 written critique
o  Receive a second level review by the National Advisory Mental Health Council

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In the 
written comments, reviewers will be asked to evaluate your 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 your application's overall 
score, weighting them as appropriate for each application.

o  Significance
o  Approach
o  Innovation
o  Investigator
o  Environment

Your 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, you may propose to carry out important work that by its nature is 
not innovative but is essential to move a field forward.

(1) SIGNIFICANCE:  Does your study address an important problem? If the aims of 
your 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?

(2) APPROACH:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of the 
project?  Do you acknowledge potential problem areas and consider alternative 
tactics?

(3) INNOVATION:  Does your project employ novel concepts, approaches or methods? 
Are the aims original and innovative?  Does your project challenge existing 
paradigms or develop new methodologies 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, your application 
will also be reviewed with respect to the following:

o  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).

o  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 included in the section on Federal 
Citations, below)

o  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.

o  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 14, 2003
Application Receipt Date:         December 18, 2003
Peer Review Date:                 February 2004
Council Review:                   May 2004
Earliest Anticipated Start Date:  August 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

DATA SAFETY AND 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: 
https://grants.nih.gov/grants/guide/notice-files/not98-084.html).

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

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

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:  
The NIH maintains a policy that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported by 
the NIH, unless there are scientific and ethical reasons not to include them.  
This policy applies to all initial (Type 1) applications submitted for receipt 
dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the inclusion of children as participants in 
research involving human subjects that is available at
https://grants.nih.gov/grants/funding/children/children.htm

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:  NIH policy 
requires education on the protection of human subject participants for all 
investigators submitting NIH proposals for research involving human subjects.  
You will find this policy announcement in the NIH Guide for Grants and Contracts 
Announcement, dated June 5, 2000, at 
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT:  The 
Office of Management and Budget (OMB) Circular A-110 has been revised to provide 
public access to research data through the Freedom of Information Act (FOIA) 
under some circumstances.  Data that are (1) first produced in a project that is 
supported in whole or in part with Federal funds and (2) cited publicly and 
officially by a Federal agency in support of an action that has the force and 
effect of law (i.e., a regulation) may be accessed through FOIA.  It is 
important for applicants to understand the basic scope of this amendment.  NIH 
has provided guidance at 
https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this 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.

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 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 https://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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