NOVEL APPROACHES TO PHENOTYPING DRUG ABUSE

RELEASE DATE:  September 15, 2003 (see addendum NOT-DA-04-001) 

RFA Number:  RFA-DA-04-005

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATIONS: 

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

COMPONENTS OF PARTICIPATING ORGANIZATIONS:
 
National Institute on Drug Abuse (NIDA) 
 (http://www.nida.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER:  93.279

LETTER OF INTENT RECEIPT DATE:  December 22, 2003
APPLICATION RECEIPT DATE:       January 22, 2004

THIS REQUEST FOR APPLICATIONS (RFA) CONTAINS THE FOLLOWING INFORMATION:

o Purpose of this RFA
o Research Objectives
o Mechanisms of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA

The National Institute on Drug Abuse (NIDA) requests applications that 
propose and evaluate novel approaches to understanding the drug abuse 
phenotype(s).  Specifically, the purpose of this initiative is to support 
innovative studies that better describe, discriminate, and predict the 
complex nature and course of drug abuse so as to offer more precise 
phenotypic indicators for testing the hypothesized underlying genetic and 
environmental risks for drug abuse.  The term "drug abuse" as used in this 
RFA refers broadly to several different but related concepts including drug 
abuse and drug dependence as defined by diagnostic criteria, as well as drug 
involvement, hazardous drug use, drug seeking behavior, and the like.  While 
it is recognized that these concepts may not be interchangeable, the term 
drug abuse is used for the purposes of fluency.  The term "drug" refers 
primarily to cannabis, cocaine, opiates, nicotine, but also includes the 
entire range of substances of abuse.  

Like other common human diseases, drug abuse is considered a "complex" 
disorder that reflects the interplay between underlying genetic 
susceptibility and environmental risk.  Despite the real promise of molecular 
genetics, there has been limited success in reliably identifying specific 
susceptibility genes for drug abuse.  Although this difficulty is often 
attributed to genetic heterogeneity, attaining greater clarity of the 
phenotypic heterogeneity of drug abuse looms large as a major challenge for 
the field.  Ultimately, the successful identification of specific genes and 
related mechanisms, underlying physiologic systems, and other etiological 
processes hinges on precise and specific phenotypic definitions and greater 
understanding of how such phenotypes influence and are shaped by 
environmental factors, developmental course, and individual characteristics.  
Although researchers and treatment providers acknowledge that drug abuse is 
diverse, complex, and dynamic, such knowledge has not been well integrated 
into research, treatment, and prevention strategies.  For example, while 
extant research conceptualizes drug abuse as a heterogeneous and dynamic 
construct, most analytic approaches operationalize drug abuse as a 
dichotomous and static outcome, and consider as covariates (or even 
statistical error) factors that may represent critical clues about drug abuse 
etiology, treatment, prevention and, ultimately, genomic search strategies.    

RESEARCH OBJECTIVES

Background

Available evidence indicates that drug abuse is a genetically and 
phenotypically complex disorder that results from the interplay between 
underlying genetic susceptibility and environmental risk.  Like many other 
relatively common human diseases, drug abuse is believed to arise from 
multiple genes exerting small effects, gene-by-gene interactions, gene-by-
environment interactions, and a host of environmental factors and risk-
conferring behaviors.  As a consequence of the multifactorial nature of drug 
abuse, the phenotypic expression is highly heterogeneous.  Drug abuse is 
heterogeneous in terms of risk factors, gender distribution and expression, 
comorbid conditions, types and number of drugs of abuse, symptom expression, 
and severity.  The course of drug abuse is a dynamic one characterized by 
patterns of persistence and remittance, drug switching and drug combinations, 
and drug preferences.  Drug abuse reflects developmental processes that 
unfold gradually over time, display continuity and discontinuity, and follow 
along multiple trajectories leading to similar or different "endpoints." Drug 
abuse is characterized by substantial individual differences with regard to 
numerous aspects including age of onset and rate of progression from initial 
drug use to persistent use, abuse, and dependence.     

Although contemporary theoretical models depict drug abuse as a heterogeneous 
and dynamic construct, this information has been comparatively less 
integrated into quantitative approaches to the study of drug abuse.  Three 
examples illustrate this point.  First, while it is well known that drug 
abusers often suffer from a range of psychiatric conditions, comorbidity is 
typically treated as a covariate to be "controlled" statistically when, 
alternatively, comorbidity may very well be an important feature of the 
outcome variable itself.  Second, drug abuse is characterized by substantial 
polysubstance involvement.  Although marijuana abusers are likely to also be 
involved with nicotine and alcohol, marijuana abuse is conventionally 
operationalized in a dichotomous fashion with little attention to the nature 
and extent of polysubstance involvement.  Furthermore, the diagnosis of 
marijuana dependence is a topic of debate that could be informed by 
alternative measures that more precisely reflect the characteristics of 
sustained marijuana involvement, such as cognitive impairment and "withdrawal 
behaviors."  Third, extant research indicates that drug abuse typically 
follows a course characterized by cyclical patterns of harmful drug use, 
remittance, and relapse.  Yet, rarely has the course of drug abuse been used 
to operationalize the drug abuse phenotype.  In sum, much prior quantitative 
research has defined drug abuse in a superficial manner whereby potentially 
critical features of drug abuse have been overlooked.  

Insofar as research over the past several decades indicates that drug abuse 
is a complex human condition that is multifaceted, future research should 
place greater emphasis on describing the defining features, influences 
shaping differential expression, and patterns of familial aggregation of the 
diverse manifestations of drug abuse.  Such a call for research takes on 
increasing importance in the context of molecular genetic studies where an 
imprecise case definition will greatly hamper the detection of risk-
conferring genes and gene-by-environment interactive effects.  Because the 
identification of gene-by-environment interactions is likely to prove key to 
understanding the etiology, prevention, and treatment of drug abuse, success 
hinges on continued refinement and advancements by epidemiologists, 
clinicians, and social scientists in identifying relatively homogeneous 
subtypes and salient behavioral (and biobehavioral) manifestations of drug 
abuse from the heterogeneous mixture of drug abuse as operationalized in 
current research.  

Areas of Interest

This initiative encourages innovative and diverse research efforts from 
multiple research disciplines including epidemiology, psychiatry, human 
development, genetic epidemiology, sociology, biostatistics, pharmacology, 
and psychology.  Projects supported through this program will be expected to 
hold promise of producing more precise and specific phenotypic definitions 
and greater understanding of how such phenotypes influence and are shaped by 
environmental factors, developmental course, and individual characteristics.  
It is hoped that the resultant scientific knowledge will aid the 
identification of specific genes and related mechanisms associated with drug 
abuse.  Examples of particular issues that would be appropriate under this 
announcement include, but are not limited to, studies that: 

o Identify common or universal behavioral manifestations of drug abuse or, 
conversely, detect reliable subtypes of drug abuse;

o Focus on dynamic (versus static) phenotypes based on course of drug use 
such as persistence of drug abuse, rate of progression from initial drug use 
to drug abuse, change in drug abuse symptomatology, and patterns of 
remittance and relapse;

o Evaluate such dynamic phenotypes according to key variables such as age of 
onset, gender, and psychiatric comorbidity;

o Employ the methods of genetic epidemiology to elucidate more precise and/or 
familial patterns, subtypes, and phenotypes of drug abuse, and ascertain the 
heritability thereof;

o Evaluate phenotypes defined in terms of consequences that are fine-tuned to 
specific drugs, such as cognitive impairment and "withdrawal behaviors" 
associated with marijuana involvement;  

o Consider polysubstance abuse, drug preferences, drug switching, and the 
role of drug availability;
 o Compare and contrast phenotypic definitions across multiple data sets, 
particular those with diverse sample characteristics and opportunities for 
drug exposure;

o Develop innovative statistical approaches to capture and evaluate the  
heterogeneity of drug abuse, particularly over time, including the use of 
latent variable approaches;

o Examine the relative salience of particular symptoms, combinations of 
symptoms, patterns and timing of psychiatric comorbidity, and extent of 
severity;

o Investigate potential "vulnerability phenotypes" or "pre-clinical markers" 
that represent indicators of specific risk for developing drug abuse;

o Inform the debate about drug abuse liability, such as the common versus 
specific liability notions of drug abuse;

o Address the salience of initial drug exposure (e.g., timing, type, amount, 
context, subjective and objective responsivity) on subsequent drug abuse risk 
and course;

o Assess potential underlying vulnerability factors or endophenotypes that 
may mediate genetic risk, including neurophysiological and temperament 
indices;

o Examine whether and how drug abuse phenotypes persist or change over time, 
across different contexts, and over generations;

o Investigate developmental influences (e.g., timing of drug exposure 
relative to developmental milestones) in the manifestation of drug abuse;

o Identify sources of drug abuse heterogeneity by gender and racial/ethnic 
group with particular focus on key dimensions of critical differences at 
individual and group levels;

Applicants are strongly encouraged to carefully consider issues related to 
statistical power.  Although projects involving primary data collection are 
appropriate for some projects, such as laboratory-based studies, applicants 
are strongly encouraged to take advantage of existing sources of data 
including epidemiologic surveys that may offer adequate sample size, enhanced 
generalizability and comparability, and considerable cost-savings.  
Applicants choosing to rely on secondary data are advised to carefully 
evaluate the appropriateness of the dataset and to discuss within the 
application the inherent strengths and limitations of the dataset to address 
their specific aims.  Applicants are also strongly encouraged to fully 
explicate and justify the statistical procedures used to address their 
specific aims.  

SPECIAL REQUIREMENTS

Annual Meetings
Principal Investigators of grants resulting from this RFA will be asked to 
participate in meetings to be convened during each funding year to report 
progress, discuss problems, and share information related to the conduct of 
their grants.  Other scientists external to and knowledgeable about these 
studies may also be invited to participate.  Requests for funds to support 
attendance at these meetings, to be held in the Washington D.C. area, should 
be included in the budget request.   

MECHANISMS OF SUPPORT

This RFA will use the NIH research project (R01), the small grant (R03) 
http://grants.nih.gov/grants/guide/pa-files/PA-03-108.html and the 
exploratory/development (R21) award mechanisms 
http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html.  As an applicant 
you will be solely responsible for planning, directing, and executing the 
proposed project.  This RFA is a one-time solicitation.  Future unsolicited, 
competing-continuation applications based on this project will compete with 
all investigator-initiated applications and will be reviewed according to the 
customary peer review procedures.  The anticipated award date is September 
30, 2004.  Applications that are not funded in the competition described in 
this RFA may be resubmitted as NEW investigator-initiated applications using 
the standard receipt dates for NEW applications described in the instructions 
to the PHS 398 application.

This RFA uses just-in-time concepts.  It also uses the modular budgeting 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 budget format.  Otherwise follow the instructions 
for non-modular budget research grant applications.  This program does not 
require cost sharing as defined in the current NIH Grants Policy Statement at 
http://grants.nih.gov/archive/grants/policy/nihgps_2001/part_i_1.htm.

FUNDS AVAILABLE 
 
NIDA intends to commit approximately $2 million in FY 2004 to fund 5 to 10 
new and/or competitive continuation grants in response to this RFA. An 
applicant may request for the R01 a project period of up to 5 years. For the 
R03, the project period is 2 years and direct costs up to $50,000 for each of 
those years.  For the R21, the project period is 2 years and up to $275,000 
in direct costs for the two year period.  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 NIDA provide support for this program, awards pursuant 
to this RFA are contingent upon the availability of funds and the receipt of 
a sufficient number of meritorious applications. 

ELIGIBLE INSTITUTIONS

You may submit (an) application(s) if your institution has any of the 
following characteristics: 

o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign institutions/organizations
o Faith-based or community-based organizations

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.   

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:

Kevin P. Conway, Ph.D.
Division of Epidemiology, Services, and Prevention Research
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Suite 5153, MSC 9589
Bethesda, MD 20892-9589
Telephone: (301) 402-1817
FAX: (301) 480-2543
Email: kconway@nida.nih.gov

o Direct your questions about peer review issues to:

Teresa Levitin, Ph.D.
Office of Extramural Affairs
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, Maryland  20892-9547
Telephone:  (301) 443-2755
FAX:  (301) 443-0538
Email:  tlevitin@mail.nih.gov

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

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Room 3131, MSC 9541
Bethesda, MD  20892-9541
Telephone:  (301) 443-6710
FAX:  (301) 594-6849
Email:  gf6s@nih.gov

As of October 18, 2003, both the Office of Extramural Affairs and the Grants 
Management Branch will move to 6101 Executive Boulevard, Bethesda, MD 20892.  
The Office of Extramural Affairs will be located in Suite 200, MSC 8401.  For 
express/courier service the address remains Rockville, MD 20852.

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 NIDA 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:

Director
Office of Extramural Affairs
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD  20892-9547
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 443-2755
FAX:  (301) 443-0538
Email:  tlevitin@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 document is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 435-0714, 
Email: GrantsInfo@nih.gov.

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications requesting 
up to $250,000 per year in direct costs must be submitted in a modular grant 
format.  The modular grant format simplifies the preparation of the budget in 
these applications by limiting the level of budgetary detail.  Applicants 
request direct costs in $25,000 modules.  Section C of the research grant 
application instructions for the PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step 
guidance for preparing modular grants.  Additional information on modular 
grants is available at 
http://grants.nih.gov/grants/funding/modular/modular.htm.
 
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) 
application form must be affixed to the bottom of the face page of the 
application.  Type the RFA number on the label.  Failure to use this label 
could result in delayed processing of the application such that it may not 
reach the review committee in time for review.  In addition, the RFA title 
and number must be typed on line 2 of the face page of the application form 
and the YES box must be marked. The RFA label is also available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
 
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of 
the application, including the Checklist, and three signed, photocopies, in 
one package to:
 
Center For Scientific Review
National Institutes Of Health/DHHS
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:

Director
Office of Extramural Affairs
National Institute on Drug Abuse/NIH/DHHS
6001 Executive Boulevard, Room 3158, MSC 9547  *
Bethesda, MD  20892-9547
Rockville, MD  20852 (for express/courier service)

*Please note change of address listed under Where to Send Inquiries Section.

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 
assignments 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 unfounded 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 the CSR and 
responsiveness by NIDA.  Incomplete applications will not be reviewed.  If 
the application is not responsive to the RFA, NIH staff may contact the 
applicant to determine whether to return the application to the applicant or 
submit it for review in competition with unsolicited applications at the next 
appropriate NIH review cycle.
 
Applications that are complete and responsive to the RFA will be evaluated 
for scientific and technical merit by an appropriate peer review group 
convened by NIDA 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 Council on Drug 
Abuse

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 the 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 the following criteria in assigning 
the application's overall score, weighting them as appropriate for each 
application. 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The application does not need to be strong in all categories to be judged 
likely to have major scientific impact and thus deserve a high priority 
score.  For example, an investigator may propose to carry out important work 
that by its nature is not innovative but is essential to move a field 
forward.

(1) SIGNIFICANCE:  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?  Does the study address an important problem consistent 
with the goals of this RFA?

(2) 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?

(3) 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?

(4) 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)?

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

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following 
items will be considered in the determination of scientific merit and the 
priority score:  

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human 
subjects and protections from research risk relating to their participation 
in the proposed research will be assessed. (See criteria included in the 
section on Federal Citations, below).

INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of 
plans to include subjects from both genders, all racial and ethnic groups 
(and subgroups), and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 
evaluated. (See Inclusion Criteria in the sections on Federal Citations, 
below).

ADDITIONAL REVIEW CONSIDERATIONS

Sharing Research Data

Applicants requesting more than $500,000 in direct costs in any year of the 
proposed research must include a data sharing plan in their application. The 
reasonableness of the data sharing plan or the rationale for not sharing 
research data will be assessed by the reviewers. However, reviewers will not 
factor the proposed data sharing plan into the determination of scientific 
merit or priority score.  (See 
http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm.)

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:  December 22, 2003 
Application Receipt Date:  January 22, 2004
Peer Review Date:  May 2004
Council Review:  September 2004
Earliest Anticipated Start Date:  September 30, 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.

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 Safety and Monitoring, NIH Guide for 
Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking more than $500,000 or 
more in direct costs in any single year are expected to include a plan for 
data sharing or state why this is not possible. 
http://grants.nih.gov/grants/policy/data_sharing. Investigators should seek 
guidance from their institutions, on issues related to institutional 
policies, local IRB rules, as well as local, state and Federal laws and 
regulations, including the Privacy Rule. Reviewers will consider the data 
sharing plan but will not factor the plan into the determination of the 
scientific merit or the priority score.

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

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

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

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

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

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

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

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

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, 
including a complete Regulation Text and a set of decision tools on "Am I a 
covered entity?"  Information on the impact of the HIPAA Privacy Rule on NIH 
processes involving the review, funding, and progress monitoring of grants, 
cooperative agreements, and research contracts can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

HIV/AIDS COUNSELING AND TESTING POLICY FOR THE NATIONAL INSTITUTE ON DRUG 
ABUSE:  Researchers funded by NIDA who are conducting research in community 
outreach settings, clinical, hospital settings, or clinical laboratories and 
have ongoing contact with clients at risk for HIV infection, are strongly 
encouraged to provide HIV risk reduction education and counseling.  HIV 
counseling should include offering HIV testing available on-site or by 
referral to other HIV testing service for persons at risk for HIV infection 
including injecting drug users, crack cocaine users, and sexually active drug 
users and their sexual partners.  For more information see 
http://grants.nih.gov/grants/guide/notice-files/NOT-DA-01-001.html.

NATIONAL ADVISORY COUNCIL ON DRUG ABUSE RECOMMENDED GUIDELINES FOR THE 
ADMINISTRATION OF DRUGS TO HUMAN SUBJECTS:  The National Advisory Council on 
Drug Abuse recognizes the importance of research involving the administration 
of drugs to human subjects and has developed guidelines relevant to such 
research.   Potential applicants are encouraged to obtain and review these 
recommendations of Council before submitting an application that will 
administer compounds to human subjects.  The guidelines are available on 
NIDA's Home Page at http://www.nida.nih.gov under the Funding, or may be 
obtained by calling (301) 443-2755.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals 
for NIH funding must be self-contained within specified page limitations. 
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites.   Furthermore, 
we caution reviewers that their anonymity may be compromised when they 
directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of "Healthy 
People 2010," a PHS-led national activity for setting priority areas. This 
RFA is related to one or more of the priority areas. Potential applicants may 
obtain a copy of "Healthy People 2010" at 
http://www.health.gov/healthypeople.

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

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


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