Part I Overview Information

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Department of Health and Human Services

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)

Title: Women, Sex/Gender Differences and Drug Abuse (R21)

Announcement Type
This is a reissue of PA-03-139, which was previously released June 16, 2003, and is now divided into separate Funding Opportunity Announcements (FOAs) for the R21, R03, and R01 grant mechanisms.

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide. 

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV.

Program Announcement (PA) Number: PA-06-331

Catalog of Federal Domestic Assistance Number(s)
93.279

Key Dates
Release/Posted Date:  April 6, 2006
Opening Date:  May 2, 2006 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): Not Applicable
NOTE: On time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Submission/Receipt Date(s):  Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm.
AIDS Application Submission/Receipt Date(s):   Please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS.
Peer Review Date(s): Please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Council Review Date(s): Please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Earliest Anticipated Start Date(s): See http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Additional Information To Be Available Date (URL Activation Date): Not Applicable
Expiration Date: June 30, 2006

Due Dates for E.O. 12372

Not Applicable.

Additional Overview Content

Executive Summary

The purpose of this Funding Opportunity Announcement (FOA) is to encourage sex/gender-based drug abuse research that focuses on the mechanisms, origins, and consequences of drug abuse, as well as prevention and treatment interventions and services. It also encourages the study of female-specific issues in all areas of drug abuse.

• 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. The total amount awarded and the number of awards are contingent upon the availability of funds and the quality, duration, and costs of the applications received.
• This FOA will use the NIH Exploratory/Developmental Research Grant (R21) award mechanism and runs in parallel with a FOA of identical scientific scope, PA-06-332, that solicits applications under the Small Research Grant (R03) award mechanism. Applicants wishing to submit applications under the traditional Research Project Grant (R01) mechanism are referred to the initial funding opportunity, PA-03-139.
• Budget and Project Period:  The total project period for an application submitted in response to this finding opportunity may not exceed two years. Direct costs are limited to $275,000 over an R21 two-year period, with no more than $200,000 in direct costs allowed in any single year. .
• Eligible Organizations: For-profit and non-profit organizations; public or private institutions, such as universities, colleges, hospitals, and laboratories; units of State and local governments; eligible agencies of the Federal government ; domestic and foreign institutions/organizations; faith-based or community-based organizations; units of State Tribal government; and units of Local Tribal government.
• Eligible Project Directors/Principal Investigators (PDs/PIs): Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are 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 support.
• Applicants may submit more than one application, provided each application is scientifically distinct.
• See Section IV.1  for application materials. The application instructions for this FOA are located at the following links: 
• http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General.doc (MS Word) 
• http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General.pdf (PDF)
• For general information on SF424 (R&R) Application and Electronic Submission, see the following Web sites:
• SF424 (R&R) Application and Electronic Submission Information: http://grants.nih.gov/grants/funding/424/index.htm
• General information on Electronic Submission of Grant Applications: http://era.nih.gov/ElectronicReceipt/
• Telecommunications for the hearing impaired is available at: TTY 301-451-5936.

Table of Contents

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Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
    1. Research Objectives

Section II. Award Information
    1. Mechanism of Support
    2. Funds Available

Section III. Eligibility Information
   1. Eligible Applicants
       A. Eligible Institutions
       B. Eligible Individuals
   2.Cost Sharing or Matching
   3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
  1. Request Application Information
  2. Content and Form of Application Submission
  3. Submission Dates and Times
      A. Submission, Review, and Anticipated Start Dates
          1. Letter of Intent
      B. Sending an Application to the NIH
      C. Application Processing
  4. Intergovernmental Review
  5. Funding Restrictions
  6. Other Submission Requirements

Section V. Application Review Information
  1. Criteria
  2. Review and Selection Process
      A. Additional Review Criteria
      B. Additional Review Considerations
      C. Sharing Research Data
      D. Sharing Research Resources
  3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
  1. Award Notices
  2. Administrative and National Policy Requirements
  3. Reporting

Section VII. Agency Contact(s)
  1. Scientific/Research Contact(s)
  2. Peer Review Contact(s)
  3. Financial/Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations


Part II - Full Text of Announcement

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Section I. Funding Opportunity Description

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1. Research Objectives

Historically, in drug abuse research, as in other fields of public health research, subjects have largely been male. Research findings emerging in the past few years, however, clearly are establishing the importance of studying issues specific to women and studying male-female differences in all areas of drug abuse research. From basic studies on genetics and neurotransmitters to studies on etiology and interventions, the scientific and clinical importance of analyzing data separately for males and females is becoming more and more evident.

Accumulating epidemiological and clinical research indicates that the predictors and progression to drug abuse and dependence are often gender-specific or are gender-sensitive.  Depression, conduct disorder, physical and sexual abuse, prenatal drug exposure and family dysfunction are among the variables differentially predictive of drug use, abuse, and dependence in males and females.  In some cases, predictors are stronger for either males or females, i.e., gender-sensitive.  In other cases, predictors apply only to males or to females, i.e., they are gender-specific.  The implications of gender-based differences in risk factors for prevention and treatment interventions are largely unexplored; however, these differences raise the possibility that interventions that are designed to target gender-sensitive and gender-specific risk factors and that are guided by well-established sex/gender differences in psychosocial and cognitive development could improve outcomes for both males and females. 

Animal and human laboratory research has shown that males and females often differ in their biological responses to drugs.  Animal studies, for example, have found male-female differences in the motor-activating effects of stimulants, speed of acquisition of drug self-administration, the amount of drug self-administered, the percentage of subjects that acquire self-administration, motivation for self-administration, and the tendency to relapse following drug cessation.  Human and animal pharmacokinetic studies often report male and female differences, as do studies of adverse effects of abused drugs.  Both human and animal studies have established that the menstrual/estrous cycle is a determinant of drug action, both pharmacokinetic and behavioral. A growing number of brain-imagining studies are reporting male-female differences. Despite the important progress made in laboratory-based sex/gender research, the work is just beginning and many questions remain unaddressed.

Numerous male-female differences in nicotine have been reported, including differences in the use patterns and dependence susceptibility, cessation rates and relapse rates, effectiveness of nicotine replacement therapies and other pharmacotherapies, control of smoking by non-nicotine factors, and the genetics of nicotine addiction including the genetic basis of nicotine metabolism.  Indeed, research on male-female differences in nicotine dependence has exceeded that of other drugs of abuse and thus may serve to guide research on other abused drugs.  Nevertheless, many gaps remain in our understanding of male-female differences in the nature of nicotine addiction and its prevention and treatment, including issues specific to females such as the menstrual cycle and weight control issues. 

According to 2004 statistics from the Centers for Disease Control and Prevention, among reported HIV cases that progress to a diagnosis of AIDS, drug abuse is associated with a greater percentage of cases among women than among men.  Over one third (37 percent) of women diagnosed with AIDS are injecting drug users (IDUs) whereas among men, 21 percent of AIDS cases are IDUs.  An additional 14 percent of women with AIDS, compared with nine percent of men with AIDS, report having sex with users who inject drugs.  Thus, in all, drug abuse is directly or indirectly associated with 51 percent of the reported AIDS cases in women compared to 30 percent of the reported cases in men. Recent research suggests that male-female related differences exist in some fundamental aspects of the HIV/AIDS disease process; for example, an HIV-infected woman with half the amount of virus circulating in the bloodstream as an infected man will progress to a diagnosis of AIDS in about the same time. Additionally numerous male-female HIV risk factors in drug abusers have been identified and there is evidence that HIV risk reduction interventions may impact men and women differently. Although drug abuse plays a greater role in HIV in women than in men, major gaps remain in knowledge regarding male-female differences in the role of drug abuse in HIV/AIDS and the unique needs of women.

Male-female differences are emerging in various aspects of treatment research including treatment entry characteristics, treatment and services needs, barriers to treatment, treatment engagement and retention, treatment outcomes, and relapse.  Such research points to the need to address the possibility that existing treatments shown to be effective for both males and females could be improved by the addition of gender-informed approaches.

The extant literature on male-female differences in drug abuse strongly suggests that males and females are likely to differ in many aspects of drug abuse yet to be explored and that in the long run, identifying and understanding such differences can improve our understanding of the nature and etiology of drug abuse and have implications for tailoring prevention and treatment interventions to maximize outcomes for both males and females.  Although progress has been made in knowledge of male-female differences in drug abuse and issues unique to women, noteworthy gaps remain.  Often, studies fail to include gender analyses, and only a small proportion of animal research includes female subjects thus providing no opportunity to analyze data for male-female differences.  Thus, in all areas of drug abuse, research is needed that examines male-female differences and issues specific to females.

In referring to differences between males and females, distinctions are often made in the use of the terms 'sex-difference' and 'gender-difference.'  In this program announcement, for brevity and because it is often not known a priori whether a difference is sex-based or gender-based, the term 'gender- difference' is sometimes used to refer to both types of differences, as is the term sex/gender difference. By convention, however, in animal research, the term sex differences is preferred over gender differences.   Additionally, researchers are encouraged to recognize that a sex/gender difference is often a proxy for an unidentified independent variable(s). Thus, finding a sex/gender difference often should be regarded as a first step in a search for such variables.

Areas of research interest for this Funding Opportunity Announcement (FOA) include, but are not limited to, the following: 

 I.  MECHANISMS AND ORIGINS:  Sex/gender differences in the basic behavioral, biological, and genetic mechanisms underlying drug abuse and dependence; and preclinical, clinical, and epidemiological studies of sex/gender differences in the determinants of initiation, progression, and maintenance of drug use and dependence.

• Studies of the genetic basis of sex/gender differences in drug abuse and dependence using a variety of methodologies, including, but not limited to, the following:  statistical or epidemiological studies to ascertain heritability; identification of genetic variants through linkage, linkage disequilibrium, or association studies; studies of candidate genes using knockout or over-expression technologies in model organisms; gene expression studies.

• Male-female differences in the biological substrates of drug abuse, including molecular, cellular, neurochemical, neuromodulatory, neuroendocrine.

• Male-female differences in the pharmacokinetics and pharmacodynamics of abused drugs.

• Male-female differences in the role of hormonal (e.g., menstrual and estrous cycle, stress hormones), psychosocial, and cognitive factors in modulating drug effects and drug use.

• Male-female differences in the developmental-organizing and activating influences of sex steroids on brain and behavior and interactions with neurotransmitter systems and the HPA axis.

• Male-female differences in the effects of stress on the response to drugs of abuse.

• Male-female differences in the abuse liability of drugs.

• Male-female differences in vulnerability to drug initiation, acquisition, escalation, dependence, and relapse. 

• Laboratory behavioral studies of male-female differences in the role of tolerance, sensitization, habituation, drug discrimination, behavioral alternatives, impulsivity, delay discounting, stress, learning, memory, and cognition in the development and maintenance of drug abuse.

• Field studies of male-female differences in the antecedents and pathways to drug abuse and dependence, including study of psychosocial and environmental risk and protective factors associated with initiation, progression, and maintenance of drug use.  

• Male-female differences in the role of psychiatric disorders (e.g., depression, PTSD, anxiety, eating disorders, borderline personality disorder, and antisocial personality) in the development and maintenance of drug abuse.  

• Male-female differences in the roles played by the timing of puberty, the transition to puberty (e.g., onset of menarche), adolescent physique characteristics, and body image distortion in the onset and progression of drug abuse. 

• Family studies of male-female differences in the intergenerational transmission of drug abuse. 

• Male-female differences in the impact of violence, victimization, and stress on psychosocial development and functioning as it relates to the development and maintenance of drug abuse and dependence.

• Male-female differences in opportunity to use drugs, access to drugs, patterns of drugs of use and abuse, and factors affecting these differences.

II. CONSEQUENCES AND IMPACT:  Laboratory (both human and animal), field, and clinical research aimed at (1) identifying male-female differences in the consequences of drug use, abuse, and addiction following acute use, chronic use, as well as residual effects following prolonged abstinence, and (2) examining drug-related consequences that are unique to females. 

• Sex/gender-specific differences in the effects of abused drugs on the nervous system, endocrine system, immune system, cardiovascular system, and other physiological systems.

• Laboratory-based studies of male-female differences in the behavioral effects of abused drugs ranging from effects on sensation, perception, and unlearned behavior (e.g., affiliative, reproductive, defensive, aggressive, ingestive) to effects on learning, conditioning, and cognition.  Studies of the biological substrates of these male-female differences. 

• Male-female differences in the perception of pain and in efficacy of both pharmacological and non-pharmacological pain treatments.

• Male-female differences in the acquisition and transmission of infection among drug users, and its clinical course and consequences.

• Sex/gender-specific medical consequences associated with drug abuse. 

• Male-female differences in the precipitation and/or exacerbation of psychiatric disorders following drug use/abuse.

• Male-female differences in the effects of drug abuse on the response to stress.

• The effects of drugs of abuse on the menstrual/estrous cycle as well as effects in the postmenopausal female. 

• The impact of drug abuse during pregnancy on medical conditions, both physiological and psychological, in the mother. 

• Male-female differences in offspring prenatally exposed to abused drugs.

• Male-female differences in the effect of drug use on the development and maintenance of interpersonal relationships, e.g., empathy, conflict, hostility, attachment, friendships, marriage.

• Male-female differences in the effect of drugs on attainment of age-appropriate developmental levels, both physiologically and psychologically.

• Male-female differences in the impact of abused drugs on aggressive, hostile and violent behavior including child abuse, sexual assault, victimization, elder abuse, and school and workplace violence.

• The effects of drugs of abuse on maternal and paternal functioning (e.g., maternal/paternal infant and child bonding, child abuse and neglect, role modeling behaviors) and differential impact on male and female offspring.

• Male-female differences in the socioeconomic and legal consequences of drug abuse, including the effects on education, employment, poverty, homelessness, gang activities, drug trafficking and distribution systems, and family functioning; (e.g., disruption, dislocation, violence, divorce and child custody.)

III.  PREVENTION AND PREVENTION SERVICES: The application of sex/gender-specific theories and empirical findings on the origins, pathways, and risk and protective factors related to drug use, progression/transition, and maintenance, to the design, development, and testing of sex/gender-based prevention strategies and interventions to determine efficacy and effectiveness.

• In universal, selective and indicated prevention programs shown to be effective, conduct gender analysis and identify the intervention features and/or components that account for gender differences in outcomes.

• Develop developmentally-appropriate gender-based universal, selective and indicated prevention strategies that are guided by etiologic research findings on sex/gender differences in risk and protective factors and by sex/gender differences in psychosocial and cognitive development.

• In family-based prevention strategies, examine the effect of gender congruence between the participating parent and child on prevention outcomes.

• Develop gender-based screening and assessment tools aimed at the identification of both risk and protective factors for use at the individual, family and community levels and in health care settings. 

• Develop interventions that consider the role of childhood and adulthood violence and victimization in perpetuating drug abuse in females with attention to environmental, psychosocial and cultural factors that keep women in the cycle of violence.

• Conduct prevention studies on the role of effective gender-specific communication in media and interpersonal interventions.

• Assess the effectiveness of gender-specific prevention services and the factors that affect their availability, adoption, adaptation, sustainability, cost benefit, and cost effectiveness.

IV.  TREATMENT AND TREATMENT SERVICES: The development and testing of theoretically-based drug treatment approaches (including behavioral treatment and pharmacotherapies) that address gender-specific issues, and the examination of gender-specific issues related to the effective and efficient delivery of drug abuse treatment services.  

• Assess the differential effectiveness of current drug abuse treatments in males and females.

• Develop and evaluate gender-based behavioral therapies and pharmacotherapies, alone and in combination in a variety of treatment settings, including traditional community-based drug treatment programs, criminal and juvenile justice settings, and primary care settings such as office-based practices and primary care clinics.

• Develop and test alternative or complementary therapies for drug abusers (e.g., biofeedback, acupuncture, herbal therapies) and compare their effectiveness in males and females.

• Examine male-female differences in therapies that target comorbid psychopathology. 

• Examine the role of sex/gender in pharmacogenetic studies. 

• Examine the efficacy and effectiveness of gender-based approaches for treatment and relapse prevention, e.g., same-sex vs. mixed-sex treatment approaches, same-sex vs. opposite-sex therapist.

• Examine gender-based treatment approaches and delivery of services for individuals having experienced violence and victimization and for those individuals with co-occurring drug abuse and mental disorders (e.g., depression, eating disorders, PTSD), and/or physical disorders (e.g., STD, HIV/AIDS, HCV).

• Develop and test family-oriented treatment approaches that are gender-specific with respect to both parents and children.

• Develop and test treatment approaches aimed at the role of partner drug use and drug treatment status in treatment outcomes.

• Identify gender-specific needs for and use of services ancillary to drug abuse treatment (e.g., childcare, transportation, housing, skills training, assertiveness training, and vocational training) and their differential impact on males and females with respect to access, utilization, retention, outcomes and cost-benefit.

• Identify effective pharmacotherapy for females of all ages including adolescence and pre-, peri- and postmenopausal women with consideration for issues such as developmental status, use of contraceptives, and use of hormone therapy. 

• Determine best treatment practices for the use of pharmacotherapy in the treatment of pregnant women and mothers who breastfeed, in terms of both the mother's and the infant's health. 

• Identify gender-based factors affecting drug abuse treatment access, treatment entry, readiness for treatment, retention in treatment, compliance with treatment, and treatment outcomes; and develop gender-based strategies to reduce or eliminate gender disparities.

• Identify organizational, management, and treatment financing practices that impede or facilitate access, utilization, retention and outcomes for female clients and assess the structure and role of organization in the development of linkages to other relevant treatment services (e.g., medical services, prenatal clinics, psychiatric services) to ensure retention and continuity of care for females, including pregnant and postpartum females.

• Develop or enhance and evaluate gender-based instruments for matching drug-abusing clients to appropriate services, and for identifying, diagnosing and assessing substance abusers in a variety of treatment settings especially primary care settings. 

V.  HIV/AIDS and RELATED INFECTIOUS DISEASES: Develop and evaluate gender-specific interventions directed at preventing and treating HIV/AIDS and related infectious diseases among drug using populations at every age level.

• Examine male-female differences in the viral, immunologic, genetic, and drug use factors that may influence susceptibility, recovery and persistence, and progression of viral diseases associated with drug use.

• Examine male-female differences in factors influencing long-term therapeutic effectiveness, development of viral resistance, disease progression, and medical outcomes.

• Examine male-female differences in the interactions/effects of antiretrovirals when used in combination with drugs of abuse and/or medication to treat drug abuse and/or medication to treat co-occurring disorders.

• Develop gender-based strategies, including behavioral and cognitive approaches, to improve access, utilization and adherence to HIV/AIDS medication regimens for drug-abusing populations both in and out of treatment.

• Develop gender-based strategies to improve clinical care and outcome with respect to antiretroviral therapy, including interventions to improve the clinical management of individuals on multiple medical therapies for HIV and associated infectious diseases. 

• Develop valid, reliable HIV/STD risk-of-exposure screening instruments with gender and age-group-specific, empirically-based normative data.

• Examine male-female differences in the behavioral dynamics and drug use-related processes associated with the acquisition and transmission of HIV and other infectious diseases, including factors that influence transitions from non-injection to injection drug use and their implications for the development of prevention interventions.

• Develop gender-based interventions to prevent HIV and other infectious diseases, including research that explores the dynamics of social networks and the identification of factors that sustain positive behavioral changes.

• Develop community-level intervention strategies aimed at preventing HIV/AIDS in women whose drug and sex practices put them at high risk of HIV infection.

CROSS-CUTTING ISSUES

In addition to the above areas of research on male-female differences and issues unique to women, several research considerations and topic areas apply to many areas of research.  They include, but are not limited to, the following:

• Research that addresses and compares stages of the life cycle, from infancy, childhood, adolescence, adulthood, to late adulthood.  

• Research that examines the role of race, ethnicity, culture, and SES in drug abuse.

• Research that examines health disparity issues in drug abuse and associated infectious diseases.

• Research on women in hidden and underserved populations, e.g., incarcerated, lesbians, transgender individuals, homeless, victims of violence, sex workers, migrant workers, school dropouts, truants, runaways, street youth, latchkey children. 

• Research on all drugs of abuse, including the nonmedical use of prescription drugs, over-the-counter drugs with abuse potential, nicotine, club drugs, and polydrug use.

• Use of a wide range of methodological approaches including longitudinal studies, secondary analyses of current data sets, descriptive and ethnographic studies, use of and development of novel measurement tools, and interdisciplinary approaches.

• Research that addresses gender-specific recruitment and retention issues. 

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

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1. Mechanism of Support

This FOA will use the NIH Exploratory/Developmental Research Grant (R21) award mechanism. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.  

This FOA uses just-in-time concepts. It also uses the modular budget formats (see the Modular Applications and Awards section of the NIH Grants Policy Statement. Specifically, if you are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 5.4, Modular Budget Component, of the Application Guide).

Exploratory/developmental grant support is for new projects only; competing renewal (formerly competing continuation ) applications will not be accepted. Up to two resubmissions (formerly revisions/amendments") of a previously reviewed exploratory/developmental grant application may be submitted. See NOT-OD-03-041, May 7, 2003.  

2. Funds Available

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 Institutes and Centers (ICs) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

The total project period for an application submitted in response to this funding opportunity may not exceed 2 years. Although the size of award may vary with the scope of research proposed, it is expected that applications will stay within the budgetary guidelines for an exploratory/developmental project; direct costs are limited to $275,000 over an R21 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, with no more than $200,000 in direct costs allowed in any single year. Applicants may request direct costs in $25,000 modules, up to the total direct costs limitation of $275,000 for the combined two-year award period. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this Program Announcement funding opportunity.

F&A costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004, November 2, 2004.

Section III. Eligibility Information

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1. Eligible Applicants

1.A. Eligible Institutions

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

• For-profit organizations
• Non-profit organizations
• Public or private institutions, such as universities, colleges, hospitals, and laboratories
• Units of State government
• Units of local government
• Eligible agencies of the Federal government
• Foreign Institutions
• Domestic Institutions
• Faith-based or community-based organizations
• Units of State Tribal government
• Units of Local Tribal government

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her 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 support.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the current NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

Applicants may submit more than one application, provided each application is scientifically distinct.

Section IV. Application and Submission Information

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Registration and Instructions for Submission via Grants.gov

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To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

• Grants.gov (http://www.grants.gov/GetStarted) and 
• eRA Commons (http://era.nih.gov/ElectronicReceipt/preparing.htm)

PD/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.

Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Started

• Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants.gov registration process.
• If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration.
• The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business days.
• Direct questions regarding Grants.gov registration to:
  Grants.gov Customer Support
  Contact Center Phone: 800-518-4726
  Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
  Email [email protected]

2) Organizational/Institutional Registration in the eRA Commons

• To find out if an organization is already Commons-registered, see the "List of Grantee Organizations Registered in NIH eRA Commons.
• Direct questions regarding the Commons registration to:
  eRA Commons Help Desk
  Phone: 301-402-7469 or 866-504-9552 (Toll Free)
  TTY: 301-451-5939
  Business hours M-F 7:00 a.m. 8:00 p.m. Eastern Time
  Email [email protected]

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

• The individual designated as the PD/PI on the application must also be registered in the NIH eRA Commons. It is not necessary for PDs/PIs to register with Grants.gov.
• The PD/PI must hold a PD/PI account in the Commons and must be affiliated with the applicant organization. This account cannot have any other role attached to it other than the PD/PI.
• This registration/affiliation must be done by the Signing Official (SO) or their designee who is already registered in the Commons.
• Both the PD/PI and SO need separate accounts in the NIH eRA Commons since both are required to verify the application.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance contact GrantsInfo, Telephone 301-710-0267, Email: [email protected].

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide (MS Word or PDF).

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see Tips and Tools for Navigating Electronic Submission on the front page of Electronic Submission of Grant Applications.

The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY will include all applicable components, required and optional. A completed application in response to this FOA will include the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget

Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

Note: While both budget components are included in the SF424 (R&R) forms package, the NIH R21 uses ONLY the PHS 398 Modular Budget. (Do not use the detailed Research & Related Budget.)

Foreign Organizations
Several special provisions apply to applications submitted by foreign organizations:

• Charge back of customs and import fees is not allowed.
• Format: Every effort should be made to comply with the format specifications, which are based upon a standard US paper size of 8.5" x 11" within each PDF.
• Funds for up to 8% administrative costs (excluding equipment) may be requested. See NOT-OD-01-028, March 29, 2001.
• Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards.
• Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI. 2. Administrative and National Policy Requirements".

Proposed research should provide a unique research opportunity not available in the United States.

3. Submission Dates and Times

See Section IV.3.A for details.

3.A. Submission, Review, and Anticipated Start Dates

Opening Date: May 2, 2006 (Earliest date an application may be submitted to Grants.gov)
Letter of Intent Receipt Date(s): Not applicable.
Application Submission Date(s): Standard Dates Apply http://grants.nih.gov/grants/funding/submissionschedule.htm
Peer Review Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
Council Review Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
Earliest Anticipated Start Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm

3.A.1. Letter of Intent

A letter of intent is not required for the funding opportunity.

3.B. Sending an Application to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow steps 1-4. Note: Applications must only be submitted electronically
PAPER APPLICATIONS WILL NOT BE ACCEPTED.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission/receipt date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image.

• If everything is acceptable, no further action is necessary. The application will automatically move forward for processing by the Division of Receipt and Referral, Center for Scientific Review, NIH, after two business days.
• Prior to the submission deadline, the AOR/SO can Reject the assembled application and submit a changed/corrected application within the two day viewing window. This option should be used if the AOR/SO determines that warnings should be addressed. Reminder: warnings do not stop further application processing. If an application submission results in warnings (but no errors) it will automatically move forward after two business days if no action is taken. Please remember that some warnings may not be applicable or may need to be addressed after application submission.
• If the two day window falls after the submission deadline, the AOR/SO will have the option to Reject the application if, due to an eRA Commons or Grants.gov system issue, the application does not correctly reflect the submitted application package (e.g., some part of the application was lost or didn t transfer correctly during the submission process). The AOR/SO should first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.
• If the AOR/SO chooses to Reject the image after the submission deadline for a reason other than an eRA Commons or Grants.gov system failure, a changed/corrected application still can be submitted but it will be subject to the NIH late policy guidelines and may not be accepted. The reason for this delay should be explained in the cover letter attachment.
• Both the AOR/SO and PD/PI will receive e-mail notifications when the application is rejected or the application automatically moves forward in the process after two days.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. Information related to the assignment of an application to a Scientific Review Group is also in the Commons. 

The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of an application already reviewed with substantial changes, but such application must include an Introduction addressing the previous critique. Note such an application is considered a "resubmission" for the SF424 (R&R).

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See the NIH Grants Policy Statement.

6. Other Submission Requirements

The NIH requires the PD/PI to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component. The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Tips and Tools for Navigating Electronic Submission on the front page of Electronic Submission of Grant Applications.

Renewal (formerly competing continuation or Type 2 ) applications are not permitted.  

All application instructions outlined in the SF424 (R&R) application are to be followed, with the following requirements for R21 applications:

• R21 applications will use the modular budget format and "Just-in-Time" concepts, with direct costs requested in $25,000 modules, up to the total direct costs limitation of $275,000 over an R21 two-year period. No more than $200,000 in direct costs will be allowed in any single year.
• Items 2-5 of the Research Plan of the R21 application may not exceed 15 pages, including tables, graphs, figures, diagrams, and charts.
• Introduction (required for a resubmission application) is limited to one page.
• Preliminary data are not required but may be included if available.

Note: While each section of the Research Plan needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.   

• R21 appendix materials should be limited, as is consistent with the exploratory nature of the R21 mechanism. The following materials may be included in the appendix:
• Up to five publications, manuscripts (accepted for publication), abstracts, patents, or other printed materials directly relevant to this project. Do not include manuscripts submitted for publication. 
  • Publications in press:  Include only a publication list with a link to the publicly available on-line journal article or the NIH PubMed Central (PMC) submission identification number.  Do not include the entire article. 
  • Manuscripts accepted for publication but not yet published: The entire article may be submitted electronically as a PDF attachment.
  • Manuscripts published but a publicly available online journal link is not available:  The entire article may be submitted electronically as a PDF attachment.
• Surveys, questionnaires, data collection instruments, clinical protocols, and informed consent documents.
• Graphic images of gels, micrographs, etc. provided that the image (may be reduced in size) is also included within the 15-page limit of Items 2-5 of the Research Plan.  No images may be included in the Appendix that are not also represented within the Research Plan.
• Do not use the Appendix to circumvent the page limitations of the Research Plan. An application that does not observe these limitations may be delayed in the review process.

Plan for Sharing Research Data

Not Applicable.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590). See Section VI.3., Reporting.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications submitted for this funding opportunity will be assigned to the ICs on the basis of established PHS referral guidelines.

Appropriate scientific review groups 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:

• 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.
• Receive a written critique.
• Receive a second level of review by the appropriate national advisory council or board.

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

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

The NIH R21 exploratory/developmental grant is a mechanism for supporting novel scientific ideas or new model systems, tools, or technologies that have the potential to significantly advance our knowledge or the status of health-related research.  Because the Research Plan is limited to 15 pages, an exploratory/developmental grant application need not have extensive background material or preliminary information as one might normally expect in an R01 application.  Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding.  Reviewers will place less emphasis on methodological details and certain indicators traditionally used in evaluating the scientific merit of R01 applications, including supportive preliminary data. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data.  Preliminary data are not required for R21 applications; however, they may be included if available.   

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application.

• Significance
• Approach
• Innovation
• Investigator
• Environment
• Additional Review Criteria

Note that an 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 scientific health problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

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

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the PD/PI and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to 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 item 6 of the Research Plan component of the SF 424 (R&R).

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 will be assessed. Plans for the recruitment and retention of subjects will also be evaluated. See item 7 of the Research Plan component of the SF 424 (R&R).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under item 11 of the Research Plan component of the SF 424 (R&R) will be assessed.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget and Period of Support: The reasonableness of the proposed budget and the appropriateness of the requested period of support in relation to the proposed research may be assessed by the reviewers. Is the percent effort listed for the PD/PI appropriate for the work proposed? Is each budget category realistic and justified in terms of the aims and methods?

2.C. Sharing Research Data

Not Applicable.

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590), See Section VI.3., Reporting.

3. Anticipated Announcement and Award Dates

Not Applicable.

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the NIH eRA Commons. 

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Section IV.5., Funding Restrictions.        

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity 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:

1. Scientific/Research Contacts:

Cora Lee Wetherington, Ph.D.
National Institute on Drug Abuse
6001 Executive Boulevard, Room 4282, MSC 9555
Bethesda, MD 20892-9555
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 434-1319
FAX: (301) 594-6043
Email: [email protected]

2. Peer Review Contacts:

Not Applicable.

3. Financial or Grants Management Contacts:

Gary Fleming, J.D.
Chief, Grants Management Branch
National Institute on Drug Abuse, NIH, DHHS
6101 Executive Boulevard, Room 270, MSC 8403
Bethesda, Maryland 20892-8403
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 443-6710
Fax: (301) 594-6849
E-mail: [email protected]

Section VIII. Other Information

Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

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 and Safety 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). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $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 and 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 scientific merit or the priority score.

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 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 funding opportunity 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.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

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 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is 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 SF424 (R&R); 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 Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

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 (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 applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process please visit the NIH Public Access Policy Web site at http://PublicAccess.nih.gov/ and view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/publicaccess_manual.htm).

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).

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 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 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.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.