GENE-ENVIRONMENT INTERACTIONS INFLUENCING ALCOHOL-RELATED PHENOTYPES AND 
DISEASES

RELEASE DATE:  June 19, 2003

PA NUMBER:  PA-03-141

March 2, 2006  (NOT-OD-06-046) – Effective with the June 1, 2006 submission date, 
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using 
the electronic SF424 (R&R) application. Parent R03 (PA-06-180) and R21 (PA-06-181) 
funding opportunity announcements have been issued for the submission date of 
June 1, 2006 and submission dates thereafter. Applications relating to R33 and R34 
activities must be in response to NIH Institute/Center (IC)-specific announcements.

EXPIRATION DATE:  May 1, 2006
 
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
 (http://www.niaaa.nih.gov) 
National Institute of Environmental Health Sciences (NIEHS)
 (http://www.niehs.nih.gov)
 
CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBERS: 93.273, 93.113, 93.114, 
93.115

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of the PA
o Research Objectives
o Mechanism(s) of Support 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS PA 

The National Institute on Alcohol Abuse and Alcoholism is seeking research 
grant applications on the role of gene-environment interactions underlying 
susceptibility to alcohol-related phenotypes including alcohol dependence, 
relapse, withdrawal; alcohol-induced organ damage including  
neurodegeneration, cirrhosis and other liver diseases, pancreatitis, 
cardiomyopathy, immune disorders, cancers, and alcohol-induced birth defects.  
This solicitation specifically encourages multidisciplinary approaches to 
study how environmental conditions, such as chemical, infectious, physical, 
nutritional, and social behavioral factors, impact genetic predisposition to 
alcohol-related diseases. Identification and characterization of gene-
environment interactions will offer better opportunities to effectively 
target prevention, intervention and treatment strategies.  The National 
Institute of Environmental Health Sciences is collaborating on this PA and is 
seeking research grant applications on interactions between alcohol effects 
and environmental agents.

RESEARCH OBJECTIVES

BACKGROUND

Alcoholism and alcohol-related diseases are the result of complex 
interactions of multiple genetic and environmental factors. Several genetic 
factors have been associated with alcohol-related behaviors, alcohol-induced 
birth defects, and alcohol-induced organ damage; however, the role of 
environmental factors in modifying the risk of developing alcohol abuse, 
alcoholism, and/or organ damage remains undefined.  

Genetic factors leading to differential risk for alcoholism were demonstrated 
using twin and family studies. In addition, functional polymorphisms of 
alcohol dehydrogenase(ADH2) and aldehyde dehydrogenase (ALDH2) genes have 
been shown to have a significant impact on alcohol metabolism in the liver, 
and thus, may contribute to vulnerability to alcohol abuse and dependence, 
alcohol-related liver diseases and cancers.

Genetic and environmental interactions modulate an individual's 
susceptibility to certain diseases/disorders.  For example, male children who 
have a polymorphism in the monoamine oxidase A gene conferring low enzyme 
activity show non aggressive behavior when raised in a non-abusive 
environment. However, male children with the same polymorphism show 
aggressive and antisocial behavior when raised in an abusive environment.  
Males with normal enzyme activity do not become violent offenders when raised 
in the same abusive/maltreated environment.  Similar results have been found 
in animals. For example, mice lacking a functional corticotroping-releasing 
hormone 1 receptor do not differ from wild-type mice in alcohol intake under 
stress-free conditions; however, after repeated stress, the knockout mice 
increase their alcohol consumption. Also, monkeys with a polymorphism in the 
regulatory region of the serotonin transporter gene show no differences from 
the wild-type monkeys when reared with their mothers. However, monkeys with 
the polymorphism that were nursery raised have attention and orientation 
deficits. 

The dynamic multi-level interactions between genetic and environmental 
components are responsible for the heterogeneity and complexity of alcohol 
dependence phenotypes. Therefore, it is necessary to use multi-disciplinary 
approaches to decipher the underlying mechanisms for alcohol abuse, alcohol 
dependence and alcohol related disorders.  Comprehensive designs and 
methodologies for both human and animal studies of gene-environment 
interactions are of crucial importance to identify alcohol-related genes and 
environmental factors, and their interrelationships. Human studies using 
informative populations such as twins, multi-generation families and 
migrants, as well as children at high risk or low risk to develop alcohol 
dependence can provide unique opportunities and advantages to study 
neurobiological and behavioral consequences of gene-environment interaction. 
In addition, animal models can be used to study gene-environment interactions 
requiring genetic and environmental manipulations that are impractical or 
ethically impossible in humans. Controlled genotypes can be devised in 
genetically modified or chemical-induced mutant animals. Therefore, animal 
models can also offer unique opportunities to explore the role of gene-
environment interactions as the means of understanding the pathways to 
alcohol-induced diseases.  

There are several approaches for analyzing the effects of environmental 
factors in experimental animals, including differential gene expression using 
cDNA microarrays, RAGE, and SAGE; as well as proteomic methods to determine 
changes in protein levels and protein modifications.  The role of genes 
implicated in the response may be further studied by developing transgenic 
and gene-targeted animals, as well as, by using other gene expression 
strategies including RNA interference (RNAi) and retroviral-mediated gene 
transfer techniques.

Epigenetic changes are known to be involved in the etiology of a large number 
of diseases such as schizophrenia, cancer, and alcohol dependence.  Recent 
evidence shows that there is an association between the GABAA receptors and 
alcohol dependence that is modulated by genetic imprinting.  There are 
numerous types of epigenetic modifications on both DNA and nucleosomes, 
including methylation and acetylation, which could affect the expression and 
regulation of alcohol-related genes.  NIAAA seeks proposals that will examine 
environmental factors that alter the epigenetic status of genes that may 
affect gene expression leading to alcohol-induced diseases.

RESARCH SCOPE

The purpose of this PA is to encourage multidisciplinary research that will 
investigate gene-environment interactions influencing susceptibility to 
alcohol abuse and dependence, alcohol-related behaviors, and alcohol-induced 
organ damage in both animals and humans.  NIAAA seeks research projects that 
include, but are not limited to: 

o studies of changes in gene or protein expression by investigating animal 
models such as knock-out and other genetically modified animals under a 
variety of environmental conditions to identify candidate genes, or their 
corresponding proteins, that may be associated with susceptibility to alcohol 
abuse and dependence, relapse, withdrawal, alcohol-induced organ damage 
including  neurodegeneration, cirrhosis and other liver diseases, 
pancreatitis, cardiomyopathy, immune disorders, cancers, and alcohol-induced 
birth defects; 

o studies to identify allelic variants (polymorphisms) and determine the 
functional relevance of an identified gene or protein for increasing or 
decreasing susceptibility to alcohol abuse and dependence, alcohol-related 
phenotypes, and other alcohol-induced diseases under different environmental 
conditions;

o studies using genetic epidemiological, psychiatric and behavioral genetic 
and molecular genetic methods to determine the interaction of genetic, 
biological, and social factors in the development of risk to alcohol abuse 
and dependence;

o studies to develop and/or utilize statistical modeling approaches to 
identify the contributions of genetic and environmental factors to the 
individual risk, their interrelationship and their developmental 
trajectories;

o studies to determine the genetic and environmental risk and protective 
factors that influence individual drinking behaviors including children and 
adolescent underage drinking across populations, socio-cultural backgrounds, 
and environmental exposures;  

o studies to determine the environmental factors that alter the epigenetic 
status of genes, thus increasing vulnerability to alcohol abuse and 
dependence, alcohol-associated behaviors, and alcohol-induced organ damage;

o studies to determine the functional relevance of candidate genomic markers 
associated with an increased susceptibility to alcohol abuse and dependence, 
alcohol-related phenotypes, and alcohol-associated medical conditions;

o studies to identify potential links between alcohol exposure and expression 
of functional polymorphisms of neurotransmitters and their receptors under 
various environmental conditions such as stress and cross-fostering, to 
understand the development of excessive drinking behaviors.

o studies to determine how genetic variations between individuals and among 
various populations impact on how environmental influences may differentially 
alter alcohol metabolism.

NIEHS seeks research grant applications in which the goals are to determine 
gene-environment effects on disease susceptibility in response to specific 
exposures or which involve Environmentally Responsive Genes, for example, as 
defined in the Environmental Genome Project (http://egp.gs.washington.edu/). 
NIEHS seeks applications that focus primarily on exposure to environmental 
agents and in which attention to alcohol abuse is secondary or minor.

MECHANISM(S) OF SUPPORT 

This PA will use the NIH R01 and Exploratory/Developmental Research Grant 
(R21) award mechanisms.  As an applicant, you will be solely responsible for 
planning, directing, and executing the proposed project.  Applications using 
the R21 mechanism may request a project period of up to two years with a 
combined budget for direct costs of up $275,000 for the two year period.  For 
example, the applicant may request $100,000 in the first year and $175,000 in 
the second year.  The request should be tailored to the needs of the project.  
Normally, no more than $200,000 may be requested in any single year.  

This PA 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.

Exploratory/developmental grant support is for new projects only; competing 
continuation applications will not be accepted. Two revisions of a previously 
reviewed exploratory/developmental grant application may be submitted as 
defined in NIH Policy at http://grants.nih.gov/grants/policy/amendedapps.htm.

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 PA and welcome the opportunity to 
answer questions from potential applicants. Inquiries may fall into two 
areas:  scientific/research and financial or grants management issues:

o Direct questions regarding human genetics and genetic variations to:

Zhaoxia Ren, M.D., Ph.D.
Program Director, Genetics and Proteomics Research Branch
Division of Basic Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 402, MSC 7003
Bethesda, MD 20892-7003
Telephone: (301) 443-5733
Fax: (301) 594-0673
Email: zren@mail.nih.gov

o Direct questions about genetic animal models and proteomics to:

Lisa A. Neuhold, Ph.D.
Program Director, Genetics and Proteomics Research Branch
Division of Basic Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 402, MSC 7003
Bethesda, MD 20892-7003
Telephone: (301) 594-6228
Fax: (301) 594-0673
Email: Lneuhold@willco.niaaa.nih.gov

o Direct questions about neuroscience and behavioral studies to: 

Ellen Witt, Ph. D.
Program Director, Neuroscience and Behavior Research Branch
Division of Basic Research
National Institute on Alcohol Abuse and Alcoholism
Willco Bldg, Suite 402
6000 Executive Blvd, MSC 7003
Bethesda, MD 20892-7003
Tel:  (301) 443-6545
Fax:  (301) 594-0673
Email:  ewitt@willco.niaaa.nih.gov

o Direct questions regarding epidemiological and statistical studies to:

Vivian B. Faden, Ph.D.
Chief, Epidemiology Branch
Division of Biometry and Epidemiology
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 402, MSC 7003
Bethesda, MD 20892-7003
Telephone: (301) 592-6232
Fax: (301) 443-8614
Email: vfaden@mail.nih.gov

o Direct questions regarding interactions between alcohol and environmental 
agents to:

Leslie Reinlib, PhD
Scientific Program Administrator
Susceptibility and Population Health Branch
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
PO Box 12233, MD-EC-21
Research Triangle Park, NC 27711
Telephone:  (919) 541-4998
Fax:        (919) 316-4606
Email: reinlib@niehs.nih.gov

o Direct inquiries regarding fiscal matters to:

Judy Fox (formerly Simons)
Chief, Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism 
6000 Executive Boulevard, Suite 504
Bethesda, MD 20892-7003
Telephone:  (301) 443-4704 
Fax:        (301) 443-3891 
Email: jsimons@willco.niaaa.nih.gov

OR

Carolyn Winters
Grants Managment Specialist
Grants Management Branch
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
PO Box 12233, MD-EC-22
Research Triangle Park, NC 27711
Telephone:  (919) 541-7823
Fax:        (919) 541-2860
Email: winters@niehs.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 
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.

APPLICATION RECEIPT DATES: Applications submitted in response to this program 
announcement will be accepted at the standard application deadlines, which 
are available at http://grants.nih.gov/grants/dates.htm.  Application 
deadlines are also indicated in the PHS 398 application kit.

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.

SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR: 
Applications requesting $500,000 or more in direct costs for any year must 
contact the proper program official identified above to receive authorization 
to submit the proposal. The applicant must include a cover letter identifying 
the NIAAA program official who has agreed to accept assignment of the 
application.   

Applicants requesting more than $500,000 must carry out the following steps:

1) Contact the IC program staff at least 6 weeks before submitting the 
application, i.e., as you are developing plans for the study; 

2) Obtain agreement from the IC staff that the IC will accept your 
application for consideration for award; and,
  
3) Identify, in a cover letter sent with the application, the staff member 
and IC who agreed to accept assignment of the application.  

This policy applies to all investigator-initiated new (type 1), competing 
continuation (type 2), competing supplement, or any amended or revised 
version of these grant application types. Additional information on this 
policy is available in the NIH Guide for Grants and Contracts, October 19, 
2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html. 

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

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

APPLICATION PROCESSING: Applications must be mailed on or before the receipt 
dates described at 
http://grants.nih.gov/grants/funding/submissionschedule.htm. The CSR will not 
accept any application in response to this PA that is essentially the same as 
one currently pending initial review unless the applicant withdraws the 
pending application.  The CSR will not accept any application that is 
essentially the same as one already reviewed.  This does not preclude the 
submission of a substantial revision of an application already reviewed, but 
such application must include an Introduction addressing the previous 
critique.  

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within 8 weeks.

PEER REVIEW PROCESS

Applications submitted for this PA will be assigned on the basis of 
established PHS referral guidelines.  An appropriate scientific review group 
convened in accordance with the standard NIH peer review procedures 
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific 
and technical merit.  

As part of the initial merit review, all applications will:

o Receive a written critique
o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score.
o Receive a second level review by an appropriate national advisory council 
or board.

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to discuss the following 
aspects of the application in order to judge the likelihood that the proposed 
research will have a substantial impact on the pursuit of these goals: 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

The scientific review group will address and consider each of these criteria 
in assigning the application's overall score, weighting them as appropriate 
for each application.  The application does not need to be strong in all 
categories to be judged likely to have major scientific impact and thus 
deserve a high priority score.  For example, an investigator may propose to 
carry out important work that by its nature is not innovative but is 
essential to move a field forward.

SIGNIFICANCE: Does this study address an important problem? If the aims of 
the application are achieved, how will scientific knowledge be advanced? What 
will be the effect of these studies on the concepts or methods that drive 
this field?

APPROACH: Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project? Does the applicant acknowledge potential problem areas and consider 
alternative tactics?

INNOVATION: Does the project employ novel concepts, approaches or methods? 
Are the aims original and innovative? Does the project challenge existing 
paradigms or develop new methodologies or technologies?

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

ENVIRONMENT: Does the scientific environment in which the work will be done 
contribute to the probability of success? Do the proposed experiments take 
advantage of unique features of the scientific environment or employ useful 
collaborative arrangements? Is there evidence of institutional support?  

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 genders, all racial and ethnic groups (and 
subgroups), and children as appropriate for the scientific goals of the 
research will be assessed.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the sections on 
Federal Citations, below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to 
be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.  

ADDITIONAL CONSIDERATIONS 

DATA SHARING:  The sharing of biological materials, interview and other 
assessment data, and genotype information (including software) in a timely 
manner has been an essential element in the rapid progress that has been made 
in the genetic analysis of human diseases.  PHS policy is that investigators 
must make unique research resources readily available for research purposes 
to qualified individuals within the scientific community when first results 
based on these resources have been published (PRINCIPLES AND GUIDELINES FOR 
RECIPIENTS OF NIH RESEARCH GRANTS AND CONTRACTS ON OBTAINING AND 
DISSEMINATING BIOMEDICAL RESEARCH RESOURCES; published on December 23, 1999 
in the Federal Register) http://www.ott.nih.gov/policy/rt_guide_final.html.  
Accordingly, to address the interests of the research community and 
government in promoting the science of the genetic basis of alcohol abuse and 
alcoholism vulnerability, NIAAA expects applicants who respond to this PA to 
develop and propose detailed plans for sharing the data and materials 
generated through the grant.

It is expected that the Data Sharing Plan will specify the following elements: 
1) creation of comprehensive and verified databases that contain all clinical, 
diagnostic, pedigree structure, and genotypic information collected and 
produced by the grant, 2) establishment of cell lines (from which DNA will be 
extracted and stored) from all protocol subjects from whom blood samples have 
been obtained, 3) a mechanism or protocol by which all databases and 
biological materials (DNA samples, cell lines) can be widely searched or 
distributed to qualified investigators in the scientific community, 4) a 
timetable specifying when various elements of the database (e.g., diagnostic, 
assessment, or genetic data) will be available for distribution.

BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

AWARD CRITERIA

Applications submitted in response to a PA will compete for available funds 
with all other recommended applications.  The following will be considered in 
making funding decisions:  

o Scientific merit of the proposed project as determined by peer review
o Availability of funds 
o Relevance to program priorities

REQUIRED FEDERAL CITATIONS 

HUMAN SUBJECTS PROTECTION:  Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against 
these risks, the potential benefits of the research to the subjects and 
others, and the importance of the knowledge gained or to be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm 

MONITORING PLAN AND DATA AND SAFETY MONITORING BOARD: Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures.  In addition, it is NIH policy 
that all clinical trials require data and safety monitoring, with the method 
and degree of monitoring being commensurate with the risks (NIH Policy for 
Data and Safety Monitoring, NIH Guide for Grants and Contracts, June 12, 
1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

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

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

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

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

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

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on 
hESCs can be found at http://stemcells.nih.gov/index.asp and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide the official NIH 
identifier(s) for the hESC line(s) to be used in the proposed research.  
Applications that do not provide this information will be returned without 
review. 

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

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  The 
Department of Health and Human Services (DHHS) issued final modification to 
the "Standards for Privacy of Individually Identifiable Health Information", 
the "Privacy Rule," on August 14, 2002.  The Privacy Rule is a federal 
regulation under the Health Insurance Portability and Accountability Act 
(HIPAA) of 1996 that governs the protection of individually identifiable 
health information, and is administered and enforced by the DHHS Office for 
Civil Rights (OCR). Those who must comply with the Privacy Rule (classified 
under the Rule as "covered entities") must do so by April 14, 2003  (with the 
exception of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including 
a complete Regulation Text and a set of decision tools on "Am I a covered 
entity?"  Information on the impact of the HIPAA Privacy Rule on NIH 
processes involving the review, funding, and progress monitoring of grants, 
cooperative agreements, and research contracts can be found at 
http://grants1.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 PA 
is related to one or more of the priority areas. Potential applicants may 
obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All 
awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants 
Policy Statement can be found at 
http://grants.nih.gov/grants/policy/policy.htm 

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, 
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in 
certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care, or early 
childhood development services are provided to children.  This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy


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