TRANSLATIONAL APPROACHES IN BIPOLAR DISORDER RESEARCH

RELEASE DATE:  August 1, 2003

RFA Number:  RFA-MH-04-004

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:  October 17, 2003

APPLICATION RECEIPT DATE:  November 17, 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 purpose of this RFA is to alert the research community to the National 
Institute of Mental Health's (NIMH) strong interest in bipolar disorder, 
particularly its key feature of cycling, and to encourage applications that 
seek to develop relevant animal models, endophenotypic markers, and 
translational research approaches that address this and related issues.  
Recognizing that scientific knowledge is rapidly enhanced when research 
questions can be addressed in both clinical populations and animal models, the 
NIMH seeks to encourage research that fosters a translational approach to the 
critically understudied area of bipolar illness.  Although potential applicants 
will not be required to have both human and animal components in their
applications, they are encouraged to identify one or more relevant aspects of 
bipolar disorder that can be modeled in both humans and animals or to focus on 
developing appropriate assessment tool(s) that can be utilized in both humans 
and animals (parallel measures).  Such measures might include 
electrophysiological, pharmacological, genetic, neuroimaging or behavioral 
techniques that can reliably quantify the targeted characteristic(s).  Research 
involving aspects of bipolar disorder that could possibly serve as the basis for 
an endophenotype, such as fluctuations in mood states or irritability, relevant 
sleep or circadian cycling, psychomotor activity levels, or other relevant 
neurobiological characteristics are of particular interest.

RESEARCH OBJECTIVES

Bipolar disorder (BD) is a severe psychiatric illness characterized by 
alternating manic and depressed mood states, with associated disturbances in 
energy levels, sleep, appetite, and cognition.  BD affects about 1% of the 
population and carries high morbidity, mortality and disability rates.  
Multiple studies indicate that about 1/3 of patients with BD suffer from 
additional comorbid personality disorders, and about 40-60% abuse one or more 
substances.  One-third of BP patients have attempted suicide at least once, and 
completed suicide rates are 20 times higher among patients with BD than in the 
general population.  Large epidemiological studies indicate that although about 
2/3 of patients with BD are unemployed, BD still represents the largest burden 
to employers in health and productivity costs relative to other mental health 
disorders, with lifetime costs estimated at $24 billion in 1998.

Although prevalence rates for BD are similar to those seen for schizophrenia, 
the NIMH receives a dramatically smaller number of research applications 
dedicated to elucidating potential mechanisms and pathophysiology of BD than it 
does for schizophrenia.  Several NIMH-sponsored workgroups have targeted bipolar 
illness as a critically understudied area and have strongly emphasized the need 
for increased research efforts.  These working groups have also recognized that 
a number of factors have made rigorous, controlled research on BD particularly 
challenging to conduct.  One major difficulty is that, by definition, BD 
symptoms shift or cycle intermittently along a spectrum of states.  Research 
becomes complicated by uncertainty as to which symptom or state is most 
profitably targeted and when, and whether the investigator's action or 
intervention has produced a given change in the patient or whether the change 
is due to the endogenous cycling.  It is clear that cycling is a key factor in 
BD pathophysiology and an important area for investigation in and of itself.

With this RFA, the NIMH seeks to build on a number of recent research findings 
that may provide important clues to fundamental questions regarding the 
mechanisms underlying BD and its key feature of cycling.  Many of these findings 
stem from research on animals, suggesting that translational approaches would 
contribute significantly towards elucidating BD pathophysiology.  Some of the 
scientific areas and approaches that may have important implications for 
understanding BD neurobiology include the following:

1.  A number of cycling or circadian phenomena that may be relevant to BD have 
been mapped out to varying degrees in animals and humans.  For example, research 
indicates that mood cycling in patients with BD may be linked to shifts in 
circadian light (both diurnal and seasonal), sleep/activity, and menstrual/
hormonal cycles.  Although substantial literature exists on the physiology of 
these specific cycles, as well as on circadian regulators like clock genes, 
little information is available on how these mechanisms might interrelate with 
or contribute specifically to BD pathophysiology.

2.  Although the nature of cycling in BD is important in itself, the essential 
symptom that cycles is mood.  Newer studies using measurements designed to 
assess or manipulate emotion and mood in humans, in conjunction with 
neurophysiological methods, have provided considerable information on the 
neurobiology relevant to these states.  This approach could productively be 
utilized more frequently in BD research, particularly if applied over time and 
across mood cycles.  In addition, the use of animals in research on mood or 
emotion is critically underdeveloped.  Assessment tools that can measure mood 
or emotion in animals, especially assessments that can be used in parallel in 
human research, would be of immense value.  The availability of such assessments 
would be expected to further enhance the development of more convincing animal 
models of mood disorders (particularly of BD), another area that is important 
but under-researched.

3.  Various second-messenger signaling pathways have been linked to the actions 
of the mood stabilizing drugs commonly used to successfully treat BD.  However, 
few studies have attempted further investigations of these effects in animal 
models or in human postmortem tissue.

4.  The current focus on identifying endophenotypes (i.e. traits associated with 
disease expression that are heritable, are present before the disease is 
manifest, and occur in unaffected relatives) has proven to be especially 
profitable for research on complex genetic diseases.  Knowledge about 
schizophrenia has advanced substantially due to recent efforts to identify 
endophenotypes for this illness.  Identifying endophenotypes for BD, which also 
has a significant genetic component with complex inheritance, would be of great 
value.  Neuroimaging, electrophysiological, neuroendocrine, and neuroimmunology 
literature suggest that BD may have unique brain structural and functional 
characteristics that could serve as endophenotypes.  This topic in BD research 
would benefit from further elaboration, as well as increased inclusion of 
first-episode patients and unaffected relatives.

Given the above, examples of potential research topics include, but are not 
limited to:

o  Mechanisms of cycling or circadian phenomena, especially as related to 
periodic changes in mood states or psychomotor activity levels.

o  Neurobiology underlying changes in vegetative functions in BD (e.g., sleep 
patterns, appetite, and stress reactivity).

o  Affect regulation (e.g., positive and negative affect, affect valence 
stability, irritability, and impulsiveness).

o  Cognitive processes, such as inhibitory control, processing of temporal cues, 
and risk assessment, that may be unique in BD.

o  Neuroimaging or postmortem studies that target identification of neural 
mechanisms underlying BD, particularly those that can also be studied in more 
detail in animal models.

o  Genetic and pharmacogenetic research linking neural mechanisms with key 
behaviors that are symptomatic of bipolar disorder.

o  Development of credible animal models of mood disorder or reliable 
assessments for emotion/mood that can be used in both animals and humans.

o  Identification of potential endophenotypes for BD, especially in studies that 
include first-episode or unaffected relative samples.

o  Investigations of BP symptoms or mechanisms that utilize data from both 
animals and humans.

In order to be judged responsive, applications submitted under this RFA must 
have clear and compelling relevance to the goal of understanding the 
neurobiological mechanisms of bipolar disorder.  Applications that propose to 
address cycling, that employ translational approaches, or that seek to identify 
potential endophenotypes will be considered of high program priority.  
Collaborations between basic and clinical scientists are encouraged.  Applicants 
are strongly encouraged to contact one of the NIH program staff listed under 
INQUIRIES with any questions regarding the responsiveness of their proposed 
project to the goals of this RFA.

MECHANISM(S) OF SUPPORT

This RFA will use the National Institutes of Health (NIH) Research Project 
Grant (R01) and the Exploratory/Developmental Grant (R21) award mechanisms 
(see https://grants.nih.gov/grants/guide/pa-files/PA-03-107.html).

Under this RFA, an applicant may request a project period of up to five years 
for R01 applications and up to three years for the R21 applications.  
Applications for the R21 award may request direct costs of up to $125,000 per 
year to support exploratory research where sufficient pilot data (that are 
ordinarily required to substantiate R01 research grant applications) are 
lacking.  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 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.  These NEW applications must be submitted on the standard 
receipt dates (https://grants.nih.gov/grants/funding/submissionschedule.htm).  
All R21 applicants who wish to resubmit their applications as R21s will also 
submit them as NEW, 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, 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 $2.5 million in FY 2004 to fund 5-10 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
o  Faith-based or community based organizations

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 scientific/research issues to:

Debra J. Babcock, Ph.D., M.D.
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7178, MSC 9639
Bethesda, MD  20892-9639
Telephone:  (301) 443-1692
FAX:  (301) 402-4740
Email:  dbabcock@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  20892-9608
Rockville, MD  20852-9608 (for express/courier service)
Telephone:  (301) 443-1340
FAX:  (301) 443-4720
Email:  kozakm@mail.nih.gov

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

Carol J. Robinson
Grants Management Branch
National Institute of Mental Health
6001 Executive Boulevard, Room 6118
Bethesda, MD  20892
Telephone:  (301) 443-3858
FAX:  (301) 443-6885
Email:  crobinso@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:

Debra J. Babcock, Ph.D., M.D.
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7178, MSC 9639
Bethesda, MD  20892-9639
Telephone:  (301) 443-1692
FAX:  (301) 402-4740
Email:  dbabcock@mail.nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  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.

SPECIFIC INSTRUCTIONS FOR MODULAR BUDGET GRANT APPLICATIONS:  Applications 
requesting up to $250,000 per year in direct costs must be submitted in a modular 
budget grant format.  The modular budget grant format simplifies the preparation of 
the budget in these applications by limiting the level of budgetary detail.  
Applicants request direct costs in $25,000 modules.  Section C of the research 
grant application instructions for the PHS 398 (rev. 5/2001) at 
https://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step 
guidance for preparing modular grants.  Additional information on modular budget 
grant applications 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 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 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 NIMH.  Incomplete applications will be returned to the 
applicant without further consideration.  And, if the application is not responsive 
to the RFA, CSR 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 
NIMH 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 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 discuss the following aspects of your 
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 your application's overall score, weighting them as appropriate for each 
application.  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.

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?

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?

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?

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)?

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:

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.

SPECIFIC R21 REVIEW CRITERIA

Innovation of the project and potential significance of the proposed research will 
be the major considerations in the evaluation of the R21 exploratory grant 
mechanism.  Because the R21 is designed to support innovative ideas, preliminary 
data as evidence of feasibility of the project are not required.  However, the 
applicant is responsible for presenting the background literature that provides 
some basis for the approach and for developing a rigorous research plan.  Relevant 
pilot data should be cited when available.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:    October 17, 2003
Application Receipt Date:         November 17, 2003
Peer Review Date:                 February 2004
Council Review:                   May 2004
Earliest Anticipated Start Date:  July 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 SAFETY AND 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 Safety and 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.

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 
https://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 approipriate, 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 
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.

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 https://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:  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 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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